Human Coronaviruses: A Review of Virus–Host Interactions
Identifieur interne : 001743 ( Pmc/Corpus ); précédent : 001742; suivant : 001744Human Coronaviruses: A Review of Virus–Host Interactions
Auteurs : Yvonne Xinyi Lim ; Yan Ling Ng ; James P. Tam ; Ding Xiang LiuSource :
- Diseases [ 2079-9721 ] ; 2016.
Abstract
Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs.
Url:
DOI: 10.3390/diseases4030026
PubMed: 28933406
PubMed Central: 5456285
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PMC:5456285Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Human Coronaviruses: A Review of Virus–Host Interactions</title><author><name sortKey="Lim, Yvonne Xinyi" sort="Lim, Yvonne Xinyi" uniqKey="Lim Y" first="Yvonne Xinyi" last="Lim">Yvonne Xinyi Lim</name></author><author><name sortKey="Ng, Yan Ling" sort="Ng, Yan Ling" uniqKey="Ng Y" first="Yan Ling" last="Ng">Yan Ling Ng</name></author><author><name sortKey="Tam, James P" sort="Tam, James P" uniqKey="Tam J" first="James P." last="Tam">James P. Tam</name></author><author><name sortKey="Liu, Ding Xiang" sort="Liu, Ding Xiang" uniqKey="Liu D" first="Ding Xiang" last="Liu">Ding Xiang Liu</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28933406</idno><idno type="pmc">5456285</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456285</idno><idno type="RBID">PMC:5456285</idno><idno type="doi">10.3390/diseases4030026</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">001743</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001743</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Human Coronaviruses: A Review of Virus–Host Interactions</title><author><name sortKey="Lim, Yvonne Xinyi" sort="Lim, Yvonne Xinyi" uniqKey="Lim Y" first="Yvonne Xinyi" last="Lim">Yvonne Xinyi Lim</name></author><author><name sortKey="Ng, Yan Ling" sort="Ng, Yan Ling" uniqKey="Ng Y" first="Yan Ling" last="Ng">Yan Ling Ng</name></author><author><name sortKey="Tam, James P" sort="Tam, James P" uniqKey="Tam J" first="James P." last="Tam">James P. Tam</name></author><author><name sortKey="Liu, Ding Xiang" sort="Liu, Ding Xiang" uniqKey="Liu D" first="Ding Xiang" last="Liu">Ding Xiang Liu</name></author></analytic><series><title level="j">Diseases</title><idno type="eISSN">2079-9721</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Pene, F" uniqKey="Pene F">F. Pene</name></author><author><name sortKey="Merlat, A" uniqKey="Merlat A">A. Merlat</name></author><author><name sortKey="Vabret, A" uniqKey="Vabret A">A. Vabret</name></author><author><name sortKey="Rozenberg, F" uniqKey="Rozenberg F">F. Rozenberg</name></author><author><name sortKey="Buzyn, A" uniqKey="Buzyn A">A. Buzyn</name></author><author><name sortKey="Dreyfus, F" uniqKey="Dreyfus F">F. Dreyfus</name></author><author><name sortKey="Cariou, A" uniqKey="Cariou A">A. Cariou</name></author><author><name sortKey="Freymuth, F" uniqKey="Freymuth F">F. Freymuth</name></author><author><name sortKey="Lebon, P" uniqKey="Lebon P">P. Lebon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vijgen, L" uniqKey="Vijgen L">L. Vijgen</name></author><author><name sortKey="Keyaerts, E" uniqKey="Keyaerts E">E. Keyaerts</name></author><author><name sortKey="Moes, E" uniqKey="Moes E">E. Moës</name></author><author><name sortKey="Maes, P" uniqKey="Maes P">P. Maes</name></author><author><name sortKey="Duson, G" uniqKey="Duson G">G. Duson</name></author><author><name sortKey="Van Ranst, M" uniqKey="Van Ranst M">M. van Ranst</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, B A" uniqKey="Jones B">B.A. Jones</name></author><author><name sortKey="Grace, D" uniqKey="Grace D">D. Grace</name></author><author><name sortKey="Kock, R" uniqKey="Kock R">R. Kock</name></author><author><name sortKey="Alonso, S" uniqKey="Alonso S">S. Alonso</name></author><author><name sortKey="Rushton, J" uniqKey="Rushton J">J. Rushton</name></author><author><name sortKey="Said, M Y" uniqKey="Said M">M.Y. Said</name></author><author><name sortKey="Mckeever, D" uniqKey="Mckeever D">D. McKeever</name></author><author><name sortKey="Mutua, F" uniqKey="Mutua F">F. Mutua</name></author><author><name sortKey="Young, J" uniqKey="Young J">J. Young</name></author><author><name sortKey="Mcdermott, J" uniqKey="Mcdermott J">J. McDermott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L. Van der Hoek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walsh, E E" uniqKey="Walsh E">E.E. Walsh 2007</name></author><author><name sortKey="Shin, J H" uniqKey="Shin J">J.H. Shin</name></author><author><name sortKey="Falsey, A R" uniqKey="Falsey A">A.R. Falsey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gorse, G J" uniqKey="Gorse G">G.J. Gorse</name></author><author><name sortKey="O Onnor, T Z" uniqKey="O Onnor T">T.Z. O’Connor</name></author><author><name sortKey="Hall, S L" uniqKey="Hall S">S.L. Hall</name></author><author><name sortKey="Vitale, J N" uniqKey="Vitale J">J.N. Vitale</name></author><author><name sortKey="Nichol, K L" uniqKey="Nichol K">K.L. Nichol</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arbour, N" uniqKey="Arbour N">N. Arbour</name></author><author><name sortKey="Day, R" uniqKey="Day R">R. Day</name></author><author><name sortKey="Newcombe, J" uniqKey="Newcombe J">J. Newcombe</name></author><author><name sortKey="Talbot, P J" uniqKey="Talbot P">P.J. Talbot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arbour, N" uniqKey="Arbour N">N. Arbour</name></author><author><name sortKey="Ekande, S" uniqKey="Ekande S">S. Ekandé</name></author><author><name sortKey="Cote, G" uniqKey="Cote G">G. Côté</name></author><author><name sortKey="Lachance, C" uniqKey="Lachance C">C. Lachance</name></author><author><name sortKey="Chagnon, F" uniqKey="Chagnon F">F. Chagnon</name></author><author><name sortKey="Tardieu, M" uniqKey="Tardieu M">M. Tardieu</name></author><author><name sortKey="Cashman, N R" uniqKey="Cashman N">N.R. Cashman</name></author><author><name sortKey="Talbot, P J" uniqKey="Talbot P">P.J. Talbot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacomy, H" uniqKey="Jacomy H">H. Jacomy</name></author><author><name sortKey="Fragoso, G" uniqKey="Fragoso G">G. Fragoso</name></author><author><name sortKey="Almazan, G" uniqKey="Almazan G">G. Almazan</name></author><author><name sortKey="Mushynski, W E" uniqKey="Mushynski W">W.E. Mushynski</name></author><author><name sortKey="Talbot, P J" uniqKey="Talbot P">P.J. Talbot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vabret, A" uniqKey="Vabret A">A. Vabret</name></author><author><name sortKey="Mourez, T" uniqKey="Mourez T">T. Mourez</name></author><author><name sortKey="Gouarin, S" uniqKey="Gouarin S">S. Gouarin</name></author><author><name sortKey="Petitjean, J" uniqKey="Petitjean J">J. Petitjean</name></author><author><name sortKey="Freymuth, F" uniqKey="Freymuth F">F. Freymuth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smuts, H" uniqKey="Smuts H">H. Smuts</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graham, R L" uniqKey="Graham R">R.L. Graham</name></author><author><name sortKey="Donaldson, E F" uniqKey="Donaldson E">E.F. Donaldson</name></author><author><name sortKey="Baric, R S" uniqKey="Baric R">R.S. Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frieman, M" uniqKey="Frieman M">M. Frieman</name></author><author><name sortKey="Baric, R" uniqKey="Baric R">R. Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, J S M" uniqKey="Peiris J">J.S.M. Peiris</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y. Guan</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, M" uniqKey="Wang M">M. Wang</name></author><author><name sortKey="Yan, M" uniqKey="Yan M">M. Yan</name></author><author><name sortKey="Xu, H" uniqKey="Xu H">H. Xu</name></author><author><name sortKey="Liang, W" uniqKey="Liang W">W. Liang</name></author><author><name sortKey="Kan, B" uniqKey="Kan B">B. Kan</name></author><author><name sortKey="Zheng, B" uniqKey="Zheng B">B. Zheng</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Zheng, H" uniqKey="Zheng H">H. Zheng</name></author><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y. Xu</name></author><author><name sortKey="Zhang, E" uniqKey="Zhang E">E. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hu, B" uniqKey="Hu B">B. Hu</name></author><author><name sortKey="Ge, X" uniqKey="Ge X">X. Ge</name></author><author><name sortKey="Wang, L F" uniqKey="Wang L">L.-F. Wang</name></author><author><name sortKey="Shi, Z" uniqKey="Shi Z">Z. Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y. Kim</name></author><author><name sortKey="Cheon, S" uniqKey="Cheon S">S. Cheon</name></author><author><name sortKey="Min, C K" uniqKey="Min C">C.-K. Min</name></author><author><name sortKey="Sohn, K M" uniqKey="Sohn K">K.M. Sohn</name></author><author><name sortKey="Kang, Y J" uniqKey="Kang Y">Y.J. Kang</name></author><author><name sortKey="Cha, Y J" uniqKey="Cha Y">Y.-J. Cha</name></author><author><name sortKey="Kang, J I" uniqKey="Kang J">J.I. Kang</name></author><author><name sortKey="Han, S K" uniqKey="Han S">S.K. Han</name></author><author><name sortKey="Ha, N Y" uniqKey="Ha N">N.Y. Ha</name></author><author><name sortKey="Kim, G" uniqKey="Kim G">G. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oboho, I K" uniqKey="Oboho I">I.K. Oboho</name></author><author><name sortKey="Tomczyk, S M" uniqKey="Tomczyk S">S.M. Tomczyk</name></author><author><name sortKey="Al Asmari, A M" uniqKey="Al Asmari A">A.M. Al-Asmari</name></author><author><name sortKey="Banjar, A A" uniqKey="Banjar A">A.A. Banjar</name></author><author><name sortKey="Al Mugti, H" uniqKey="Al Mugti H">H. Al-Mugti</name></author><author><name sortKey="Aloraini, M S" uniqKey="Aloraini M">M.S. Aloraini</name></author><author><name sortKey="Alkhaldi, K Z" uniqKey="Alkhaldi K">K.Z. Alkhaldi</name></author><author><name sortKey="Almohammadi, E L" uniqKey="Almohammadi E">E.L. Almohammadi</name></author><author><name sortKey="Alraddadi, B M" uniqKey="Alraddadi B">B.M. Alraddadi</name></author><author><name sortKey="Gerber, S I" uniqKey="Gerber S">S.I. Gerber</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Masters, P S" uniqKey="Masters P">P.S. Masters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcbride, R" uniqKey="Mcbride R">R. McBride</name></author><author><name sortKey="Fielding, B C" uniqKey="Fielding B">B.C. Fielding</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gorbalenya, A E" uniqKey="Gorbalenya A">A.E. Gorbalenya</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E.J. Snijder</name></author><author><name sortKey="Spaan, W J M" uniqKey="Spaan W">W.J.M. Spaan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kolesnikova, L" uniqKey="Kolesnikova L">L. Kolesnikova</name></author><author><name sortKey="Slenczka, W" uniqKey="Slenczka W">W. Slenczka</name></author><author><name sortKey="Brodt, H" uniqKey="Brodt H">H. Brodt</name></author><author><name sortKey="Klenk, H" uniqKey="Klenk H">H. Klenk</name></author><author><name sortKey="Becker, S" uniqKey="Becker S">S. Becker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marsolais, G" uniqKey="Marsolais G">G. Marsolais</name></author><author><name sortKey="Berthiaume, L" uniqKey="Berthiaume L">L. Berthiaume</name></author><author><name sortKey="Difranco, E" uniqKey="Difranco E">E. DiFranco</name></author><author><name sortKey="Marois, P" uniqKey="Marois P">P. Marois</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, D X" uniqKey="Liu D">D.X. Liu</name></author><author><name sortKey="Fung, T S" uniqKey="Fung T">T.S. Fung</name></author><author><name sortKey="Chong, K K L" uniqKey="Chong K">K.K.-L. Chong</name></author><author><name sortKey="Shukla, A" uniqKey="Shukla A">A. Shukla</name></author><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R. Hilgenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yeager, C L" uniqKey="Yeager C">C.L. Yeager</name></author><author><name sortKey="Ashmun, R A" uniqKey="Ashmun R">R.A. Ashmun</name></author><author><name sortKey="Williams, R K" uniqKey="Williams R">R.K. Williams</name></author><author><name sortKey="Cardellichio, C B" uniqKey="Cardellichio C">C.B. Cardellichio</name></author><author><name sortKey="Shapiro, L H" uniqKey="Shapiro L">L.H. Shapiro</name></author><author><name sortKey="Look, A T" uniqKey="Look A">A.T. Look</name></author><author><name sortKey="Holmes, K V" uniqKey="Holmes K">K.V. Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Moore, M J" uniqKey="Moore M">M.J. Moore</name></author><author><name sortKey="Vasilieva, N" uniqKey="Vasilieva N">N. Vasilieva</name></author><author><name sortKey="Sui, J" uniqKey="Sui J">J. Sui</name></author><author><name sortKey="Wong, S K" uniqKey="Wong S">S.K. Wong</name></author><author><name sortKey="Berne, M A" uniqKey="Berne M">M.A. Berne</name></author><author><name sortKey="Somasundaran, M" uniqKey="Somasundaran M">M. Somasundaran</name></author><author><name sortKey="Sullivan, J L" uniqKey="Sullivan J">J.L. Sullivan</name></author><author><name sortKey="Luzuriaga, K" uniqKey="Luzuriaga K">K. Luzuriaga</name></author><author><name sortKey="Greenough, T C" uniqKey="Greenough T">T.C. Greenough</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Sui, J" uniqKey="Sui J">J. Sui</name></author><author><name sortKey="Huang, I C" uniqKey="Huang I">I.C. Huang</name></author><author><name sortKey="Kuhn, J H" uniqKey="Kuhn J">J.H. Kuhn</name></author><author><name sortKey="Radoshitzky, S R" uniqKey="Radoshitzky S">S.R. Radoshitzky</name></author><author><name sortKey="Marasco, W A" uniqKey="Marasco W">W.A. Marasco</name></author><author><name sortKey="Choe, H" uniqKey="Choe H">H. Choe</name></author><author><name sortKey="Farzan, M" uniqKey="Farzan M">M. Farzan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, K" uniqKey="Wu K">K. Wu</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Peng, G" uniqKey="Peng G">G. Peng</name></author><author><name sortKey="Li, F" uniqKey="Li F">F. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N. Van Doremalen</name></author><author><name sortKey="Miazgowicz, K L" uniqKey="Miazgowicz K">K.L. Miazgowicz</name></author><author><name sortKey="Milne Price, S" uniqKey="Milne Price S">S. Milne-Price</name></author><author><name sortKey="Bushmaker, T" uniqKey="Bushmaker T">T. Bushmaker</name></author><author><name sortKey="Robertson, S" uniqKey="Robertson S">S. Robertson</name></author><author><name sortKey="Scott, D" uniqKey="Scott D">D. Scott</name></author><author><name sortKey="Kinne, J" uniqKey="Kinne J">J. Kinne</name></author><author><name sortKey="Mclellan, J S" uniqKey="Mclellan J">J.S. McLellan</name></author><author><name sortKey="Zhu, J" uniqKey="Zhu J">J. Zhu</name></author><author><name sortKey="Munster, V J" uniqKey="Munster V">V.J. Munster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, X" uniqKey="Huang X">X. Huang</name></author><author><name sortKey="Dong, W" uniqKey="Dong W">W. Dong</name></author><author><name sortKey="Milewska, A" uniqKey="Milewska A">A. Milewska</name></author><author><name sortKey="Golda, A" uniqKey="Golda A">A. Golda</name></author><author><name sortKey="Qi, Y" uniqKey="Qi Y">Y. Qi</name></author><author><name sortKey="Zhu, Q K" uniqKey="Zhu Q">Q.K. Zhu</name></author><author><name sortKey="Marasco, W A" uniqKey="Marasco W">W.A. Marasco</name></author><author><name sortKey="Baric, R S" uniqKey="Baric R">R.S. Baric</name></author><author><name sortKey="Sims, A C" uniqKey="Sims A">A.C. Sims</name></author><author><name sortKey="Pyrc, K" uniqKey="Pyrc K">K. Pyrc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Butler, N" uniqKey="Butler N">N. Butler</name></author><author><name sortKey="Pewe, L" uniqKey="Pewe L">L. Pewe</name></author><author><name sortKey="Trandem, K" uniqKey="Trandem K">K. Trandem</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author><author><name sortKey="Chan, J W" uniqKey="Chan J">J.W. Chan</name></author><author><name sortKey="Azhar, E I" uniqKey="Azhar E">E.I. Azhar</name></author><author><name sortKey="Hui, D C" uniqKey="Hui D">D.C. Hui</name></author><author><name sortKey="Yuen, K" uniqKey="Yuen K">K. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bosch, B J" uniqKey="Bosch B">B.J. Bosch</name></author><author><name sortKey="Bartelink, W" uniqKey="Bartelink W">W. Bartelink</name></author><author><name sortKey="Rottier, P J M" uniqKey="Rottier P">P.J.M. Rottier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qian, Z" uniqKey="Qian Z">Z. Qian</name></author><author><name sortKey="Dominguez, S R" uniqKey="Dominguez S">S.R. Dominguez</name></author><author><name sortKey="Holmes, K V" uniqKey="Holmes K">K.V. Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simmons, G" uniqKey="Simmons G">G. Simmons</name></author><author><name sortKey="Gosalia, D N" uniqKey="Gosalia D">D.N. Gosalia</name></author><author><name sortKey="Rennekamp, A J" uniqKey="Rennekamp A">A.J. Rennekamp</name></author><author><name sortKey="Reeves, J D" uniqKey="Reeves J">J.D. Reeves</name></author><author><name sortKey="Diamond, S L" uniqKey="Diamond S">S.L. Diamond</name></author><author><name sortKey="Bates, P" uniqKey="Bates P">P. Bates</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bertram, S" uniqKey="Bertram S">S. Bertram</name></author><author><name sortKey="Dijkman, R" uniqKey="Dijkman R">R. Dijkman</name></author><author><name sortKey="Habjan, M" uniqKey="Habjan M">M. Habjan</name></author><author><name sortKey="Heurich, A" uniqKey="Heurich A">A. Heurich</name></author><author><name sortKey="Gierer, S" uniqKey="Gierer S">S. Gierer</name></author><author><name sortKey="Glowacka, I" uniqKey="Glowacka I">I. Glowacka</name></author><author><name sortKey="Welsch, K" uniqKey="Welsch K">K. Welsch</name></author><author><name sortKey="Winkler, M" uniqKey="Winkler M">M. Winkler</name></author><author><name sortKey="Schneider, H" uniqKey="Schneider H">H. Schneider</name></author><author><name sortKey="Hofmann Winkler, H" uniqKey="Hofmann Winkler H">H. Hofmann-Winkler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bertram, S" uniqKey="Bertram S">S. Bertram</name></author><author><name sortKey="Glowacka, I" uniqKey="Glowacka I">I. Glowacka</name></author><author><name sortKey="Muller, M A" uniqKey="Muller M">M.A. Müller</name></author><author><name sortKey="Lavender, H" uniqKey="Lavender H">H. Lavender</name></author><author><name sortKey="Gnirss, K" uniqKey="Gnirss K">K. Gnirss</name></author><author><name sortKey="Nehlmeier, I" uniqKey="Nehlmeier I">I. Nehlmeier</name></author><author><name sortKey="Niemeyer, D" uniqKey="Niemeyer D">D. Niemeyer</name></author><author><name sortKey="He, Y" uniqKey="He Y">Y. He</name></author><author><name sortKey="Simmons, G" uniqKey="Simmons G">G. Simmons</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Millet, J K" uniqKey="Millet J">J.K. Millet</name></author><author><name sortKey="Whittaker, G R" uniqKey="Whittaker G">G.R. Whittaker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, I C" uniqKey="Huang I">I.C. Huang</name></author><author><name sortKey="Bailey, C C" uniqKey="Bailey C">C.C. Bailey</name></author><author><name sortKey="Weyer, J L" uniqKey="Weyer J">J.L. Weyer</name></author><author><name sortKey="Radoshitzky, S R" uniqKey="Radoshitzky S">S.R. Radoshitzky</name></author><author><name sortKey="Becker, M M" uniqKey="Becker M">M.M. Becker</name></author><author><name sortKey="Chiang, J J" uniqKey="Chiang J">J.J. Chiang</name></author><author><name sortKey="Brass, A L" uniqKey="Brass A">A.L. Brass</name></author><author><name sortKey="Ahmed, A A" uniqKey="Ahmed A">A.A. Ahmed</name></author><author><name sortKey="Chi, X" uniqKey="Chi X">X. Chi</name></author><author><name sortKey="Dong, L" uniqKey="Dong L">L. Dong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, K" uniqKey="Li K">K. Li</name></author><author><name sortKey="Markosyan, R M" uniqKey="Markosyan R">R.M. Markosyan</name></author><author><name sortKey="Zheng, Y M" uniqKey="Zheng Y">Y.-M. Zheng</name></author><author><name sortKey="Golfetto, O" uniqKey="Golfetto O">O. Golfetto</name></author><author><name sortKey="Bungart, B" uniqKey="Bungart B">B. Bungart</name></author><author><name sortKey="Li, M" uniqKey="Li M">M. Li</name></author><author><name sortKey="Ding, S" uniqKey="Ding S">S. Ding</name></author><author><name sortKey="He, Y" uniqKey="He Y">Y. He</name></author><author><name sortKey="Liang, C" uniqKey="Liang C">C. Liang</name></author><author><name sortKey="Lee, J C" uniqKey="Lee J">J.C. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luo, H" uniqKey="Luo H">H. Luo</name></author><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q. Chen</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name></author><author><name sortKey="Chen, K" uniqKey="Chen K">K. Chen</name></author><author><name sortKey="Shen, X" uniqKey="Shen X">X. Shen</name></author><author><name sortKey="Jiang, H" uniqKey="Jiang H">H. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nanda, S K" uniqKey="Nanda S">S.K. Nanda</name></author><author><name sortKey="Leibowitz, J L" uniqKey="Leibowitz J">J.L. Leibowitz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, C H" uniqKey="Wu C">C.-H. Wu</name></author><author><name sortKey="Chen, P J" uniqKey="Chen P">P.-J. Chen</name></author><author><name sortKey="Yeh, S H" uniqKey="Yeh S">S.-H. Yeh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, Y W" uniqKey="Tan Y">Y.W. Tan</name></author><author><name sortKey="Hong, W" uniqKey="Hong W">W. Hong</name></author><author><name sortKey="Liu, D X" uniqKey="Liu D">D.X. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neuman, B W" uniqKey="Neuman B">B.W. Neuman</name></author><author><name sortKey="Kiss, G" uniqKey="Kiss G">G. Kiss</name></author><author><name sortKey="Kunding, A H" uniqKey="Kunding A">A.H. Kunding</name></author><author><name sortKey="Bhella, D" uniqKey="Bhella D">D. Bhella</name></author><author><name sortKey="Baksh, M F" uniqKey="Baksh M">M.F. Baksh</name></author><author><name sortKey="Connelly, S" uniqKey="Connelly S">S. Connelly</name></author><author><name sortKey="Droese, B" uniqKey="Droese B">B. Droese</name></author><author><name sortKey="Klaus, J P" uniqKey="Klaus J">J.P. Klaus</name></author><author><name sortKey="Makino, S" uniqKey="Makino S">S. Makino</name></author><author><name sortKey="Sawicki, S G" uniqKey="Sawicki S">S.G. Sawicki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luo, H" uniqKey="Luo H">H. Luo</name></author><author><name sortKey="Wu, D" uniqKey="Wu D">D. Wu</name></author><author><name sortKey="Shen, C" uniqKey="Shen C">C. Shen</name></author><author><name sortKey="Chen, K" uniqKey="Chen K">K. Chen</name></author><author><name sortKey="Shen, X" uniqKey="Shen X">X. Shen</name></author><author><name sortKey="Jiang, H" uniqKey="Jiang H">H. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wong, H H" uniqKey="Wong H">H.H. Wong</name></author><author><name sortKey="Kumar, P" uniqKey="Kumar P">P. Kumar</name></author><author><name sortKey="Tay, F P L" uniqKey="Tay F">F.P.L. Tay</name></author><author><name sortKey="Moreau, D" uniqKey="Moreau D">D. Moreau</name></author><author><name sortKey="Liu, D X" uniqKey="Liu D">D.X. Liu</name></author><author><name sortKey="Bard, F" uniqKey="Bard F">F. Bard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kerr, J F R" uniqKey="Kerr J">J.F.R. Kerr</name></author><author><name sortKey="Wyllie, A H" uniqKey="Wyllie A">A.H. Wyllie</name></author><author><name sortKey="Currie, A R" uniqKey="Currie A">A.R. Currie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boulares, A H" uniqKey="Boulares A">A.H. Boulares</name></author><author><name sortKey="Yakovlev, A G" uniqKey="Yakovlev A">A.G. Yakovlev</name></author><author><name sortKey="Ivanova, V" uniqKey="Ivanova V">V. Ivanova</name></author><author><name sortKey="Stoica, B A" uniqKey="Stoica B">B.A. Stoica</name></author><author><name sortKey="Wang, G" uniqKey="Wang G">G. Wang</name></author><author><name sortKey="Iyer, S" uniqKey="Iyer S">S. Iyer</name></author><author><name sortKey="Smulson, M" uniqKey="Smulson M">M. Smulson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Segawa, K" uniqKey="Segawa K">K. Segawa</name></author><author><name sortKey="Kurata, S" uniqKey="Kurata S">S. Kurata</name></author><author><name sortKey="Yanagihashi, Y" uniqKey="Yanagihashi Y">Y. Yanagihashi</name></author><author><name sortKey="Brummelkamp, T R" uniqKey="Brummelkamp T">T.R. Brummelkamp</name></author><author><name sortKey="Matsuda, F" uniqKey="Matsuda F">F. Matsuda</name></author><author><name sortKey="Nagata, S" uniqKey="Nagata S">S. Nagata</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walczak, H" uniqKey="Walczak H">H. Walczak</name></author><author><name sortKey="Krammer, P H" uniqKey="Krammer P">P.H. Krammer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bender, L M" uniqKey="Bender L">L.M. Bender</name></author><author><name sortKey="Morgan, M J" uniqKey="Morgan M">M.J. Morgan</name></author><author><name sortKey="Thomas, L R" uniqKey="Thomas L">L.R. Thomas</name></author><author><name sortKey="Liu, Z G" uniqKey="Liu Z">Z.G. Liu</name></author><author><name sortKey="Thorburn, A" uniqKey="Thorburn A">A. Thorburn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stennicke, H R" uniqKey="Stennicke H">H.R. Stennicke</name></author><author><name sortKey="Jurgensmeier, J M" uniqKey="Jurgensmeier J">J.M. Jürgensmeier</name></author><author><name sortKey="Shin, H" uniqKey="Shin H">H. Shin</name></author><author><name sortKey="Deveraux, Q" uniqKey="Deveraux Q">Q. Deveraux</name></author><author><name sortKey="Wolf, B B" uniqKey="Wolf B">B.B. Wolf</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X. Yang</name></author><author><name sortKey="Zhou, Q" uniqKey="Zhou Q">Q. Zhou</name></author><author><name sortKey="Ellerby, H M" uniqKey="Ellerby H">H.M. Ellerby</name></author><author><name sortKey="Ellerby, L M" uniqKey="Ellerby L">L.M. Ellerby</name></author><author><name sortKey="Bredesen, D" uniqKey="Bredesen D">D. Bredesen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taylor, R C" uniqKey="Taylor R">R.C. Taylor</name></author><author><name sortKey="Cullen, S P" uniqKey="Cullen S">S.P. Cullen</name></author><author><name sortKey="Martin, S J" uniqKey="Martin S">S.J. Martin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sebbagh, M" uniqKey="Sebbagh M">M. Sebbagh</name></author><author><name sortKey="Renvoize, C" uniqKey="Renvoize C">C. Renvoize</name></author><author><name sortKey="Hamelin, J" uniqKey="Hamelin J">J. Hamelin</name></author><author><name sortKey="Riche, N" uniqKey="Riche N">N. Riche</name></author><author><name sortKey="Bertoglio, J" uniqKey="Bertoglio J">J. Bertoglio</name></author><author><name sortKey="Breard, J" uniqKey="Breard J">J. Breard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, H" uniqKey="Li H">H. Li</name></author><author><name sortKey="Zhu, H" uniqKey="Zhu H">H. Zhu</name></author><author><name sortKey="Xu, C J" uniqKey="Xu C">C.-J. Xu</name></author><author><name sortKey="Yuan, J" uniqKey="Yuan J">J. Yuan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Benedict, C A" uniqKey="Benedict C">C.A. Benedict</name></author><author><name sortKey="Norris, P S" uniqKey="Norris P">P.S. Norris</name></author><author><name sortKey="Ware, C F" uniqKey="Ware C">C.F. Ware</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kvansakul, M" uniqKey="Kvansakul M">M. Kvansakul</name></author><author><name sortKey="Hinds, M G" uniqKey="Hinds M">M.G. Hinds</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pearce, A F" uniqKey="Pearce A">A.F. Pearce</name></author><author><name sortKey="Lyles, D S" uniqKey="Lyles D">D.S. Lyles</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aillet, F" uniqKey="Aillet F">F. Aillet</name></author><author><name sortKey="Masutani, H" uniqKey="Masutani H">H. Masutani</name></author><author><name sortKey="Elbim, C" uniqKey="Elbim C">C. Elbim</name></author><author><name sortKey="Raoul, H" uniqKey="Raoul H">H. Raoul</name></author><author><name sortKey="Chene, L" uniqKey="Chene L">L. Chêne</name></author><author><name sortKey="Nugeyre, M T" uniqKey="Nugeyre M">M.T. Nugeyre</name></author><author><name sortKey="Paya, C" uniqKey="Paya C">C. Paya</name></author><author><name sortKey="Barre Sinoussi, F" uniqKey="Barre Sinoussi F">F. Barré-Sinoussi</name></author><author><name sortKey="Gougerot Pocidalo, M A" uniqKey="Gougerot Pocidalo M">M.A. Gougerot-Pocidalo</name></author><author><name sortKey="Israel, N" uniqKey="Israel N">N. Israël</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tamura, R" uniqKey="Tamura R">R. Tamura</name></author><author><name sortKey="Kanda, T" uniqKey="Kanda T">T. Kanda</name></author><author><name sortKey="Imazeki, F" uniqKey="Imazeki F">F. Imazeki</name></author><author><name sortKey="Wu, S" uniqKey="Wu S">S. Wu</name></author><author><name sortKey="Nakamoto, S" uniqKey="Nakamoto S">S. Nakamoto</name></author><author><name sortKey="Tanaka, T" uniqKey="Tanaka T">T. Tanaka</name></author><author><name sortKey="Arai, M" uniqKey="Arai M">M. Arai</name></author><author><name sortKey="Fujiwara, K" uniqKey="Fujiwara K">K. Fujiwara</name></author><author><name sortKey="Saito, K" uniqKey="Saito K">K. Saito</name></author><author><name sortKey="Roger, T" uniqKey="Roger T">T. Roger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aweya, J J" uniqKey="Aweya J">J.J. Aweya</name></author><author><name sortKey="Sze, C W" uniqKey="Sze C">C.W. Sze</name></author><author><name sortKey="Bayega, A" uniqKey="Bayega A">A. Bayega</name></author><author><name sortKey="Mohd Ismail, N K" uniqKey="Mohd Ismail N">N.K. Mohd-Ismail</name></author><author><name sortKey="Deng, L" uniqKey="Deng L">L. Deng</name></author><author><name sortKey="Hotta, H" uniqKey="Hotta H">H. Hotta</name></author><author><name sortKey="Tan, Y J" uniqKey="Tan Y">Y.J. Tan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nakamura Lopez, Y" uniqKey="Nakamura Lopez Y">Y. Nakamura-Lopez</name></author><author><name sortKey="Villegas Sepulveda, N" uniqKey="Villegas Sepulveda N">N. Villegas-Sepúlveda</name></author><author><name sortKey="G Mez, B" uniqKey="G Mez B">B. Gómez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mocarski, E S" uniqKey="Mocarski E">E.S. Mocarski</name></author><author><name sortKey="Upton, J W" uniqKey="Upton J">J.W. Upton</name></author><author><name sortKey="Kaiser, W J" uniqKey="Kaiser W">W.J. Kaiser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amara, A" uniqKey="Amara A">A. Amara</name></author><author><name sortKey="Mercer, J" uniqKey="Mercer J">J. Mercer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Collins, A R" uniqKey="Collins A">A.R. Collins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pyrc, K" uniqKey="Pyrc K">K. Pyrc</name></author><author><name sortKey="Berkhout, B" uniqKey="Berkhout B">B. Berkhout</name></author><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L. van der Hoek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gu, J" uniqKey="Gu J">J. Gu</name></author><author><name sortKey="Korteweg, C" uniqKey="Korteweg C">C. Korteweg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tao, X" uniqKey="Tao X">X. Tao</name></author><author><name sortKey="Hill, T E" uniqKey="Hill T">T.E. Hill</name></author><author><name sortKey="Morimoto, C" uniqKey="Morimoto C">C. Morimoto</name></author><author><name sortKey="Peters, C J" uniqKey="Peters C">C.J. Peters</name></author><author><name sortKey="Ksiazek, T G" uniqKey="Ksiazek T">T.G. Ksiazek</name></author><author><name sortKey="Tseng, C T K" uniqKey="Tseng C">C.-T.K. Tseng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yeung, M L" uniqKey="Yeung M">M.-L. Yeung</name></author><author><name sortKey="Yao, Y" uniqKey="Yao Y">Y. Yao</name></author><author><name sortKey="Jia, L" uniqKey="Jia L">L. Jia</name></author><author><name sortKey="Chan, J F W" uniqKey="Chan J">J.F.W. Chan</name></author><author><name sortKey="Chan, K H" uniqKey="Chan K">K.-H. Chan</name></author><author><name sortKey="Cheung, K F" uniqKey="Cheung K">K.-F. Cheung</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Poon, V K M" uniqKey="Poon V">V.K.M. Poon</name></author><author><name sortKey="Tsang, A K L" uniqKey="Tsang A">A.K.L. Tsang</name></author><author><name sortKey="To, K K W" uniqKey="To K">K.K.W. To</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Desforges, M" uniqKey="Desforges M">M. Desforges</name></author><author><name sortKey="Coupanec, A" uniqKey="Coupanec A">A. Coupanec</name></author><author><name sortKey="Brison, E" uniqKey="Brison E">É. Brison</name></author><author><name sortKey="Meessen Pinard, M" uniqKey="Meessen Pinard M">M. Meessen-Pinard</name></author><author><name sortKey="Talbot, P J" uniqKey="Talbot P">P.J. Talbot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Desforges, M" uniqKey="Desforges M">M. Desforges</name></author><author><name sortKey="Le Coupanec, A" uniqKey="Le Coupanec A">A. Le Coupanec</name></author><author><name sortKey="Stodola, J K" uniqKey="Stodola J">J.K. Stodola</name></author><author><name sortKey="Meessen Pinard, M" uniqKey="Meessen Pinard M">M. Meessen-Pinard</name></author><author><name sortKey="Talbot, P J" uniqKey="Talbot P">P.J. Talbot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Favreau, D J" uniqKey="Favreau D">D.J. Favreau</name></author><author><name sortKey="Meessen Pinard, M" uniqKey="Meessen Pinard M">M. Meessen-Pinard</name></author><author><name sortKey="Desforges, M" uniqKey="Desforges M">M. Desforges</name></author><author><name sortKey="Talbot, P J" uniqKey="Talbot P">P.J. Talbot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kr Hling, V" uniqKey="Kr Hling V">V. Krähling</name></author><author><name sortKey="Stein, D A" uniqKey="Stein D">D.A. Stein</name></author><author><name sortKey="Spiegel, M" uniqKey="Spiegel M">M. Spiegel</name></author><author><name sortKey="Weber, F" uniqKey="Weber F">F. Weber</name></author><author><name sortKey="Muhlberger, E" uniqKey="Muhlberger E">E. Mühlberger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Collins, A R" uniqKey="Collins A">A.R. Collins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y. Yang</name></author><author><name sortKey="Xiong, Z" uniqKey="Xiong Z">Z. Xiong</name></author><author><name sortKey="Zhang, S" uniqKey="Zhang S">S. Zhang</name></author><author><name sortKey="Yan, Y" uniqKey="Yan Y">Y. Yan</name></author><author><name sortKey="Nguyen, J" uniqKey="Nguyen J">J. Nguyen</name></author><author><name sortKey="Ng, B" uniqKey="Ng B">B. Ng</name></author><author><name sortKey="Lu, H" uniqKey="Lu H">H. Lu</name></author><author><name sortKey="Brendese, J" uniqKey="Brendese J">J. Brendese</name></author><author><name sortKey="Yang, F" uniqKey="Yang F">F. Yang</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ying, T" uniqKey="Ying T">T. Ying</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Dimitrov, D S" uniqKey="Dimitrov D">D.S. Dimitrov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chu, H" uniqKey="Chu H">H. Chu</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J. Zhou</name></author><author><name sortKey="Wong, B H Y" uniqKey="Wong B">B.H.-Y. Wong</name></author><author><name sortKey="Li, C" uniqKey="Li C">C. Li</name></author><author><name sortKey="Chan, J F W" uniqKey="Chan J">J.F.-W. Chan</name></author><author><name sortKey="Cheng, Z S" uniqKey="Cheng Z">Z.-S. Cheng</name></author><author><name sortKey="Yang, D" uniqKey="Yang D">D. Yang</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D. Wang</name></author><author><name sortKey="Lee, A C" uniqKey="Lee A">A.C. Lee</name></author><author><name sortKey="Li, C" uniqKey="Li C">C. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mesel Lemoine, M" uniqKey="Mesel Lemoine M">M. Mesel-Lemoine</name></author><author><name sortKey="Millet, J" uniqKey="Millet J">J. Millet</name></author><author><name sortKey="Vidalain, P O" uniqKey="Vidalain P">P.-O. Vidalain</name></author><author><name sortKey="Law, H" uniqKey="Law H">H. Law</name></author><author><name sortKey="Vabret, A" uniqKey="Vabret A">A. Vabret</name></author><author><name sortKey="Lorin, V" uniqKey="Lorin V">V. Lorin</name></author><author><name sortKey="Escriou, N" uniqKey="Escriou N">N. Escriou</name></author><author><name sortKey="Albert, M L" uniqKey="Albert M">M.L. Albert</name></author><author><name sortKey="Nal, B" uniqKey="Nal B">B. Nal</name></author><author><name sortKey="Tangy, F" uniqKey="Tangy F">F. Tangy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spiegel, M" uniqKey="Spiegel M">M. Spiegel</name></author><author><name sortKey="Schneider, K" uniqKey="Schneider K">K. Schneider</name></author><author><name sortKey="Weber, F" uniqKey="Weber F">F. Weber</name></author><author><name sortKey="Weidmann, M" uniqKey="Weidmann M">M. Weidmann</name></author><author><name sortKey="Hufert, F" uniqKey="Hufert F">F. Hufert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bordi, L" uniqKey="Bordi L">L. Bordi</name></author><author><name sortKey="Castilletti, C" uniqKey="Castilletti C">C. Castilletti</name></author><author><name sortKey="Falasca, L" uniqKey="Falasca L">L. Falasca</name></author><author><name sortKey="Ciccosanti, F" uniqKey="Ciccosanti F">F. Ciccosanti</name></author><author><name sortKey="Calcaterra, S" uniqKey="Calcaterra S">S. Calcaterra</name></author><author><name sortKey="Rozera, G" uniqKey="Rozera G">G. Rozera</name></author><author><name sortKey="Di Caro, A" uniqKey="Di Caro A">A. Di Caro</name></author><author><name sortKey="Zaniratti, S" uniqKey="Zaniratti S">S. Zaniratti</name></author><author><name sortKey="Rinaldi, A" uniqKey="Rinaldi A">A. Rinaldi</name></author><author><name sortKey="Ippolito, G" uniqKey="Ippolito G">G. Ippolito</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ren, L" uniqKey="Ren L">L. Ren</name></author><author><name sortKey="Yang, R" uniqKey="Yang R">R. Yang</name></author><author><name sortKey="Guo, L" uniqKey="Guo L">L. Guo</name></author><author><name sortKey="Qu, J" uniqKey="Qu J">J. Qu</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Hung, T" uniqKey="Hung T">T. Hung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, B S F" uniqKey="Tang B">B.S.F. Tang</name></author><author><name sortKey="Chan, K H" uniqKey="Chan K">K.-h. Chan</name></author><author><name sortKey="Cheng, V C C" uniqKey="Cheng V">V.C.C. Cheng</name></author><author><name sortKey="Woo, P C Y" uniqKey="Woo P">P.C.Y. Woo</name></author><author><name sortKey="Lau, S K P" uniqKey="Lau S">S.K.P. Lau</name></author><author><name sortKey="Lam, C C K" uniqKey="Lam C">C.C.K. Lam</name></author><author><name sortKey="Chan, T L" uniqKey="Chan T">T.L. Chan</name></author><author><name sortKey="Wu, A K" uniqKey="Wu A">A.K. Wu</name></author><author><name sortKey="Hung, I F" uniqKey="Hung I">I.F. Hung</name></author><author><name sortKey="Leung, S Y" uniqKey="Leung S">S.Y. Leung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chow, K Y C" uniqKey="Chow K">K.Y.C. Chow</name></author><author><name sortKey="Yeung, Y S" uniqKey="Yeung Y">Y.S. Yeung</name></author><author><name sortKey="Hon, C C" uniqKey="Hon C">C.C. Hon</name></author><author><name sortKey="Zeng, F" uniqKey="Zeng F">F. Zeng</name></author><author><name sortKey="Law, K M" uniqKey="Law K">K.M. Law</name></author><author><name sortKey="Leung, F C C" uniqKey="Leung F">F.C.C. Leung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Surjit, M" uniqKey="Surjit M">M. Surjit</name></author><author><name sortKey="Liu, B" uniqKey="Liu B">B. Liu</name></author><author><name sortKey="Jameel, S" uniqKey="Jameel S">S. Jameel</name></author><author><name sortKey="Chow, V T K" uniqKey="Chow V">V.T.K. Chow</name></author><author><name sortKey="Lal, S K" uniqKey="Lal S">S.K. Lal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, Y J" uniqKey="Tan Y">Y.-J. Tan</name></author><author><name sortKey="Fielding, B C" uniqKey="Fielding B">B.C. Fielding</name></author><author><name sortKey="Goh, P Y" uniqKey="Goh P">P.-Y. Goh</name></author><author><name sortKey="Shen, S" uniqKey="Shen S">S. Shen</name></author><author><name sortKey="Tan, T H P" uniqKey="Tan T">T.H.P. Tan</name></author><author><name sortKey="Lim, S G" uniqKey="Lim S">S.G. Lim</name></author><author><name sortKey="Hong, W" uniqKey="Hong W">W. Hong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ye, Z" uniqKey="Ye Z">Z. Ye</name></author><author><name sortKey="Wong, C K" uniqKey="Wong C">C.K. Wong</name></author><author><name sortKey="Li, P" uniqKey="Li P">P. Li</name></author><author><name sortKey="Xie, Y" uniqKey="Xie Y">Y. Xie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sharma, K" uniqKey="Sharma K">K. Sharma</name></author><author><name sortKey=" Kerstrom, S" uniqKey=" Kerstrom S">S. Åkerström</name></author><author><name sortKey="Sharma, A K" uniqKey="Sharma A">A.K. Sharma</name></author><author><name sortKey="Chow, V T K" uniqKey="Chow V">V.T.K. Chow</name></author><author><name sortKey="Teow, S" uniqKey="Teow S">S. Teow</name></author><author><name sortKey="Abrenica, B" uniqKey="Abrenica B">B. Abrenica</name></author><author><name sortKey="Booth, S A" uniqKey="Booth S">S.A. Booth</name></author><author><name sortKey="Booth, T F" uniqKey="Booth T">T.F. Booth</name></author><author><name sortKey="Mirazimi, A" uniqKey="Mirazimi A">A. Mirazimi</name></author><author><name sortKey="Lal, S K" uniqKey="Lal S">S.K. Lal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tsoi, H" uniqKey="Tsoi H">H. Tsoi</name></author><author><name sortKey="Li, L" uniqKey="Li L">L. Li</name></author><author><name sortKey="Chen, Zhefan S" uniqKey="Chen Z">Zhefan S. Chen</name></author><author><name sortKey="Lau, K F" uniqKey="Lau K">K.-F. Lau</name></author><author><name sortKey="Tsui, S K W" uniqKey="Tsui S">S.K.W. Tsui</name></author><author><name sortKey="Chan, H Y E" uniqKey="Chan H">H.Y.E. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Diego, M L" uniqKey="De Diego M">M.L. De Diego</name></author><author><name sortKey="Nieto Torres, J L" uniqKey="Nieto Torres J">J.L. Nieto-Torres</name></author><author><name sortKey="Jimenez Guarde O, J M" uniqKey="Jimenez Guarde O J">J.M. JimÈnez-GuardeÒo</name></author><author><name sortKey="Regla Nava, J A" uniqKey="Regla Nava J">J.A. Regla-Nava</name></author><author><name sortKey="Alvarez, E" uniqKey="Alvarez E">E. Álvarez</name></author><author><name sortKey="Oliveros, J C" uniqKey="Oliveros J">J.C. Oliveros</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J. Zhao</name></author><author><name sortKey="Fett, C" uniqKey="Fett C">C. Fett</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author><author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L. Enjuanes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, Y X" uniqKey="Tan Y">Y.-X. Tan</name></author><author><name sortKey="Tan, T H P" uniqKey="Tan T">T.H.P. Tan</name></author><author><name sortKey="Lee, M J R" uniqKey="Lee M">M.J.R. Lee</name></author><author><name sortKey="Tham, P Y" uniqKey="Tham P">P.-Y. Tham</name></author><author><name sortKey="Gunalan, V" uniqKey="Gunalan V">V. Gunalan</name></author><author><name sortKey="Druce, J" uniqKey="Druce J">J. Druce</name></author><author><name sortKey="Birch, C" uniqKey="Birch C">C. Birch</name></author><author><name sortKey="Catton, M" uniqKey="Catton M">M. Catton</name></author><author><name sortKey="Fu, N Y" uniqKey="Fu N">N.Y. Fu</name></author><author><name sortKey="Yu, V C" uniqKey="Yu V">V.C. Yu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Favreau, D J" uniqKey="Favreau D">D.J. Favreau</name></author><author><name sortKey="Desforges, M" uniqKey="Desforges M">M. Desforges</name></author><author><name sortKey="St Jean, J R" uniqKey="St Jean J">J.R. St-Jean</name></author><author><name sortKey="Talbot, P J" uniqKey="Talbot P">P.J. Talbot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Diemer, C" uniqKey="Diemer C">C. Diemer</name></author><author><name sortKey="Schneider, M" uniqKey="Schneider M">M. Schneider</name></author><author><name sortKey="Seebach, J" uniqKey="Seebach J">J. Seebach</name></author><author><name sortKey="Quaas, J" uniqKey="Quaas J">J. Quaas</name></author><author><name sortKey="Frosner, G" uniqKey="Frosner G">G. Frösner</name></author><author><name sortKey="Sch Tzl, H M" uniqKey="Sch Tzl H">H.M. Schätzl</name></author><author><name sortKey="Gilch, S" uniqKey="Gilch S">S. Gilch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alcami, A" uniqKey="Alcami A">A. Alcami</name></author><author><name sortKey="Koszinowski, U H" uniqKey="Koszinowski U">U.H. Koszinowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bowie, A G" uniqKey="Bowie A">A.G. Bowie</name></author><author><name sortKey="Unterholzner, L" uniqKey="Unterholzner L">L. Unterholzner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawai, T" uniqKey="Kawai T">T. Kawai</name></author><author><name sortKey="Akira, S" uniqKey="Akira S">S. Akira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jensen, S" uniqKey="Jensen S">S. Jensen</name></author><author><name sortKey="Thomsen, A R" uniqKey="Thomsen A">A.R. Thomsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, S M Y" uniqKey="Lee S">S.M.Y. Lee</name></author><author><name sortKey="Kok, K H" uniqKey="Kok K">K.-H. Kok</name></author><author><name sortKey="Jaume, M" uniqKey="Jaume M">M. Jaume</name></author><author><name sortKey="Cheung, T K W" uniqKey="Cheung T">T.K.W. Cheung</name></author><author><name sortKey="Yip, T F" uniqKey="Yip T">T.-F. Yip</name></author><author><name sortKey="Lai, J C C" uniqKey="Lai J">J.C.C. Lai</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y. Guan</name></author><author><name sortKey="Webster, R G" uniqKey="Webster R">R.G. Webster</name></author><author><name sortKey="Jin, D Y" uniqKey="Jin D">D.Y. Jin</name></author><author><name sortKey="Peiris, J S" uniqKey="Peiris J">J.S. Peiris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weber, F" uniqKey="Weber F">F. Weber</name></author><author><name sortKey="Wagner, V" uniqKey="Wagner V">V. Wagner</name></author><author><name sortKey="Rasmussen, S B" uniqKey="Rasmussen S">S.B. Rasmussen</name></author><author><name sortKey="Hartmann, R" uniqKey="Hartmann R">R. Hartmann</name></author><author><name sortKey="Paludan, S R" uniqKey="Paludan S">S.R. Paludan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hemmi, H" uniqKey="Hemmi H">H. Hemmi</name></author><author><name sortKey="Takeuchi, O" uniqKey="Takeuchi O">O. Takeuchi</name></author><author><name sortKey="Kawai, T" uniqKey="Kawai T">T. Kawai</name></author><author><name sortKey="Kaisho, T" uniqKey="Kaisho T">T. Kaisho</name></author><author><name sortKey="Sato, S" uniqKey="Sato S">S. Sato</name></author><author><name sortKey="Sanjo, H" uniqKey="Sanjo H">H. Sanjo</name></author><author><name sortKey="Matsumoto, M" uniqKey="Matsumoto M">M. Matsumoto</name></author><author><name sortKey="Hoshino, K" uniqKey="Hoshino K">K. Hoshino</name></author><author><name sortKey="Wagner, H" uniqKey="Wagner H">H. Wagner</name></author><author><name sortKey="Takeda, K" uniqKey="Takeda K">K. Takeda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Krug, A" uniqKey="Krug A">A. Krug</name></author><author><name sortKey="Luker, G D" uniqKey="Luker G">G.D. Luker</name></author><author><name sortKey="Barchet, W" uniqKey="Barchet W">W. Barchet</name></author><author><name sortKey="Leib, D A" uniqKey="Leib D">D.A. Leib</name></author><author><name sortKey="Akira, S" uniqKey="Akira S">S. Akira</name></author><author><name sortKey="Colonna, M" uniqKey="Colonna M">M. Colonna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Krug, A" uniqKey="Krug A">A. Krug</name></author><author><name sortKey="French, A R" uniqKey="French A">A.R. French</name></author><author><name sortKey="Barchet, W" uniqKey="Barchet W">W. Barchet</name></author><author><name sortKey="Fischer, J A A" uniqKey="Fischer J">J.A.A. Fischer</name></author><author><name sortKey="Dzionek, A" uniqKey="Dzionek A">A. Dzionek</name></author><author><name sortKey="Pingel, J T" uniqKey="Pingel J">J.T. Pingel</name></author><author><name sortKey="Orihuela, M M" uniqKey="Orihuela M">M.M. Orihuela</name></author><author><name sortKey="Akira, S" uniqKey="Akira S">S. Akira</name></author><author><name sortKey="Yokoyama, W M" uniqKey="Yokoyama W">W.M. Yokoyama</name></author><author><name sortKey="Colonna, M" uniqKey="Colonna M">M. Colonna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoffmann, M" uniqKey="Hoffmann M">M. Hoffmann</name></author><author><name sortKey="Zeisel, M B" uniqKey="Zeisel M">M.B. Zeisel</name></author><author><name sortKey="Jilg, N" uniqKey="Jilg N">N. Jilg</name></author><author><name sortKey="Paranhos Baccala, G" uniqKey="Paranhos Baccala G">G. Paranhos-Baccalà</name></author><author><name sortKey="Stoll Keller, F" uniqKey="Stoll Keller F">F. Stoll-Keller</name></author><author><name sortKey="Wakita, T" uniqKey="Wakita T">T. Wakita</name></author><author><name sortKey="Hafkemeyer, P" uniqKey="Hafkemeyer P">P. Hafkemeyer</name></author><author><name sortKey="Blum, H E" uniqKey="Blum H">H.E. Blum</name></author><author><name sortKey="Barth, H" uniqKey="Barth H">H. Barth</name></author><author><name sortKey="Henneke, P" uniqKey="Henneke P">P. Henneke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bieback, K" uniqKey="Bieback K">K. Bieback</name></author><author><name sortKey="Lien, E" uniqKey="Lien E">E. Lien</name></author><author><name sortKey="Klagge, I M" uniqKey="Klagge I">I.M. Klagge</name></author><author><name sortKey="Avota, E" uniqKey="Avota E">E. Avota</name></author><author><name sortKey="Schneider Schaulies, J" uniqKey="Schneider Schaulies J">J. Schneider-Schaulies</name></author><author><name sortKey="Duprex, W P" uniqKey="Duprex W">W.P. Duprex</name></author><author><name sortKey="Wagner, H" uniqKey="Wagner H">H. Wagner</name></author><author><name sortKey="Kirschning, C J" uniqKey="Kirschning C">C.J. Kirschning</name></author><author><name sortKey="Ter Meulen, V" uniqKey="Ter Meulen V">V. Ter Meulen</name></author><author><name sortKey="Schneider Schaulies, S" uniqKey="Schneider Schaulies S">S. Schneider-Schaulies</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rallabhandi, P" uniqKey="Rallabhandi P">P. Rallabhandi</name></author><author><name sortKey="Phillips, R L" uniqKey="Phillips R">R.L. Phillips</name></author><author><name sortKey="Boukhvalova, M S" uniqKey="Boukhvalova M">M.S. Boukhvalova</name></author><author><name sortKey="Pletneva, L M" uniqKey="Pletneva L">L.M. Pletneva</name></author><author><name sortKey="Shirey, K A" uniqKey="Shirey K">K.A. Shirey</name></author><author><name sortKey="Gioannini, T L" uniqKey="Gioannini T">T.L. Gioannini</name></author><author><name sortKey="Weiss, J P" uniqKey="Weiss J">J.P. Weiss</name></author><author><name sortKey="Chow, J C" uniqKey="Chow J">J.C. Chow</name></author><author><name sortKey="Hawkins, L D" uniqKey="Hawkins L">L.D. Hawkins</name></author><author><name sortKey="Vogel, S N" uniqKey="Vogel S">S.N. Vogel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ben Haij, N" uniqKey="Ben Haij N">N. Ben Haij</name></author><author><name sortKey="Leghmari, K" uniqKey="Leghmari K">K. Leghmari</name></author><author><name sortKey="Planes, R" uniqKey="Planes R">R. Planès</name></author><author><name sortKey="Thieblemont, N" uniqKey="Thieblemont N">N. Thieblemont</name></author><author><name sortKey="Bahraoui, E" uniqKey="Bahraoui E">E. Bahraoui</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kumar, H" uniqKey="Kumar H">H. Kumar</name></author><author><name sortKey="Kawai, T" uniqKey="Kawai T">T. Kawai</name></author><author><name sortKey="Akira, S" uniqKey="Akira S">S. Akira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Honda, K" uniqKey="Honda K">K. Honda</name></author><author><name sortKey="Taniguchi, T" uniqKey="Taniguchi T">T. Taniguchi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brown, J" uniqKey="Brown J">J. Brown</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H. Wang</name></author><author><name sortKey="Hajishengallis, G N" uniqKey="Hajishengallis G">G.N. Hajishengallis</name></author><author><name sortKey="Martin, M" uniqKey="Martin M">M. Martin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Eill, L A J" uniqKey="O Eill L">L.A.J. O’Neill</name></author><author><name sortKey="Golenbock, D" uniqKey="Golenbock D">D. Golenbock</name></author><author><name sortKey="Bowie, A G" uniqKey="Bowie A">A.G. Bowie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoneyama, M" uniqKey="Yoneyama M">M. Yoneyama</name></author><author><name sortKey="Kikuchi, M" uniqKey="Kikuchi M">M. Kikuchi</name></author><author><name sortKey="Matsumoto, K" uniqKey="Matsumoto K">K. Matsumoto</name></author><author><name sortKey="Imaizumi, T" uniqKey="Imaizumi T">T. Imaizumi</name></author><author><name sortKey="Miyagishi, M" uniqKey="Miyagishi M">M. Miyagishi</name></author><author><name sortKey="Taira, K" uniqKey="Taira K">K. Taira</name></author><author><name sortKey="Foy, E" uniqKey="Foy E">E. Foy</name></author><author><name sortKey="Loo, Y M" uniqKey="Loo Y">Y.M. Loo</name></author><author><name sortKey="Gale, M" uniqKey="Gale M">M. Gale</name></author><author><name sortKey="Akira, S" uniqKey="Akira S">S. Akira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rodriguez, K R" uniqKey="Rodriguez K">K.R. Rodriguez</name></author><author><name sortKey="Bruns, A M" uniqKey="Bruns A">A.M. Bruns</name></author><author><name sortKey="Horvath, C M" uniqKey="Horvath C">C.M. Horvath</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Satoh, T" uniqKey="Satoh T">T. Satoh</name></author><author><name sortKey="Kato, H" uniqKey="Kato H">H. Kato</name></author><author><name sortKey="Kumagai, Y" uniqKey="Kumagai Y">Y. Kumagai</name></author><author><name sortKey="Yoneyama, M" uniqKey="Yoneyama M">M. Yoneyama</name></author><author><name sortKey="Sato, S" uniqKey="Sato S">S. Sato</name></author><author><name sortKey="Matsushita, K" uniqKey="Matsushita K">K. Matsushita</name></author><author><name sortKey="Tsujimura, T" uniqKey="Tsujimura T">T. Tsujimura</name></author><author><name sortKey="Fujita, T" uniqKey="Fujita T">T. Fujita</name></author><author><name sortKey="Akira, S" uniqKey="Akira S">S. Akira</name></author><author><name sortKey="Takeuchi, O" uniqKey="Takeuchi O">O. Takeuchi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, Z" uniqKey="Zhu Z">Z. Zhu</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X. Zhang</name></author><author><name sortKey="Wang, G" uniqKey="Wang G">G. Wang</name></author><author><name sortKey="Zheng, H" uniqKey="Zheng H">H. Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, G" uniqKey="Liu G">G. Liu</name></author><author><name sortKey="Park, H S" uniqKey="Park H">H.-S. Park</name></author><author><name sortKey="Pyo, H M" uniqKey="Pyo H">H.-M. Pyo</name></author><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q. Liu</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y. Zhou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gack, M U" uniqKey="Gack M">M.U. Gack</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kanneganti, T D" uniqKey="Kanneganti T">T.-D. Kanneganti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guo, H" uniqKey="Guo H">H. Guo</name></author><author><name sortKey="Callaway, J B" uniqKey="Callaway J">J.B. Callaway</name></author><author><name sortKey="Ting, J P Y" uniqKey="Ting J">J.P.Y. Ting</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ivashkiv, L B" uniqKey="Ivashkiv L">L.B. Ivashkiv</name></author><author><name sortKey="Donlin, L T" uniqKey="Donlin L">L.T. Donlin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schoggins, J W" uniqKey="Schoggins J">J.W. Schoggins</name></author><author><name sortKey="Rice, C M" uniqKey="Rice C">C.M. Rice</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kindler, E" uniqKey="Kindler E">E. Kindler</name></author><author><name sortKey="J Nsd Ttir, H R" uniqKey="J Nsd Ttir H">H.R. Jónsdóttir</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D. Muth</name></author><author><name sortKey="Hamming, O J" uniqKey="Hamming O">O.J. Hamming</name></author><author><name sortKey="Hartmann, R" uniqKey="Hartmann R">R. Hartmann</name></author><author><name sortKey="Rodriguez, R" uniqKey="Rodriguez R">R. Rodriguez</name></author><author><name sortKey="Geffers, R" uniqKey="Geffers R">R. Geffers</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R.A. Fouchier</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Muller, M A" uniqKey="Muller M">M.A. Müller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frieman, M" uniqKey="Frieman M">M. Frieman</name></author><author><name sortKey="Heise, M" uniqKey="Heise M">M. Heise</name></author><author><name sortKey="Baric, R" uniqKey="Baric R">R. Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clementz, M A" uniqKey="Clementz M">M.A. Clementz</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z. Chen</name></author><author><name sortKey="Banach, B S" uniqKey="Banach B">B.S. Banach</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Sun, L" uniqKey="Sun L">L. Sun</name></author><author><name sortKey="Ratia, K" uniqKey="Ratia K">K. Ratia</name></author><author><name sortKey="Baez Santos, Y M" uniqKey="Baez Santos Y">Y.M. Baez-Santos</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Takayama, J" uniqKey="Takayama J">J. Takayama</name></author><author><name sortKey="Ghosh, A K" uniqKey="Ghosh A">A.K. Ghosh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, S K P" uniqKey="Lau S">S.K.P. Lau</name></author><author><name sortKey="Lau, C C Y" uniqKey="Lau C">C.C.Y. Lau</name></author><author><name sortKey="Chan, K H" uniqKey="Chan K">K.-H. Chan</name></author><author><name sortKey="Li, C P Y" uniqKey="Li C">C.P.Y. Li</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Jin, D Y" uniqKey="Jin D">D.-Y. Jin</name></author><author><name sortKey="Chan, J F" uniqKey="Chan J">J.F. Chan</name></author><author><name sortKey="Woo, P C" uniqKey="Woo P">P.C. Woo</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheung, C Y" uniqKey="Cheung C">C.Y. Cheung</name></author><author><name sortKey="Poon, L L M" uniqKey="Poon L">L.L.M. Poon</name></author><author><name sortKey="Ng, I H Y" uniqKey="Ng I">I.H.Y. Ng</name></author><author><name sortKey="Luk, W" uniqKey="Luk W">W. Luk</name></author><author><name sortKey="Sia, S F" uniqKey="Sia S">S.-F. Sia</name></author><author><name sortKey="Wu, M H S" uniqKey="Wu M">M.H.S. Wu</name></author><author><name sortKey="Chan, K H" uniqKey="Chan K">K.H. Chan</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.Y. Yuen</name></author><author><name sortKey="Gordon, S" uniqKey="Gordon S">S. Gordon</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y. Guan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Randall, R E" uniqKey="Randall R">R.E. Randall</name></author><author><name sortKey="Goodbourn, S" uniqKey="Goodbourn S">S. Goodbourn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Funk, C J" uniqKey="Funk C">C.J. Funk</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Ito, Y" uniqKey="Ito Y">Y. Ito</name></author><author><name sortKey="Travanty, E A" uniqKey="Travanty E">E.A. Travanty</name></author><author><name sortKey="Voelker, D R" uniqKey="Voelker D">D.R. Voelker</name></author><author><name sortKey="Holmes, K V" uniqKey="Holmes K">K.V. Holmes</name></author><author><name sortKey="Mason, R J" uniqKey="Mason R">R.J. Mason</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gosert, R" uniqKey="Gosert R">R. Gosert</name></author><author><name sortKey="Kanjanahaluethai, A" uniqKey="Kanjanahaluethai A">A. Kanjanahaluethai</name></author><author><name sortKey="Egger, D" uniqKey="Egger D">D. Egger</name></author><author><name sortKey="Bienz, K" uniqKey="Bienz K">K. Bienz</name></author><author><name sortKey="Baker, S C" uniqKey="Baker S">S.C. Baker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author><author><name sortKey="Netland, J" uniqKey="Netland J">J. Netland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Siu, K L" uniqKey="Siu K">K.L. Siu</name></author><author><name sortKey="Kok, K H" uniqKey="Kok K">K.H. Kok</name></author><author><name sortKey="Ng, M H" uniqKey="Ng M">M.H. Ng</name></author><author><name sortKey="Poon, V K" uniqKey="Poon V">V.K. Poon</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.Y. Yuen</name></author><author><name sortKey="Zheng, B J" uniqKey="Zheng B">B.J. Zheng</name></author><author><name sortKey="Jin, D Y" uniqKey="Jin D">D.Y. Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Siu, K L" uniqKey="Siu K">K.-L. Siu</name></author><author><name sortKey="Chan, C P" uniqKey="Chan C">C.-P. Chan</name></author><author><name sortKey="Kok, K H" uniqKey="Kok K">K.-H. Kok</name></author><author><name sortKey="Chiu Yat Woo, P" uniqKey="Chiu Yat Woo P">P. Chiu-Yat Woo</name></author><author><name sortKey="Jin, D Y" uniqKey="Jin D">D.-Y. Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y. Yang</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name></author><author><name sortKey="Geng, H" uniqKey="Geng H">H. Geng</name></author><author><name sortKey="Deng, Y" uniqKey="Deng Y">Y. Deng</name></author><author><name sortKey="Huang, B" uniqKey="Huang B">B. Huang</name></author><author><name sortKey="Guo, Y" uniqKey="Guo Y">Y. Guo</name></author><author><name sortKey="Zhao, Z" uniqKey="Zhao Z">Z. Zhao</name></author><author><name sortKey="Tan, W" uniqKey="Tan W">W. Tan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kopecky Bromberg, S A" uniqKey="Kopecky Bromberg S">S.A. Kopecky-Bromberg</name></author><author><name sortKey="Martinez Sobrido, L" uniqKey="Martinez Sobrido L">L. Martínez-Sobrido</name></author><author><name sortKey="Frieman, M" uniqKey="Frieman M">M. Frieman</name></author><author><name sortKey="Baric, R A" uniqKey="Baric R">R.A. Baric</name></author><author><name sortKey="Palese, P" uniqKey="Palese P">P. Palese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, X" uniqKey="Lu X">X. Lu</name></author><author><name sortKey="Pan, J A" uniqKey="Pan J">J.A. Pan</name></author><author><name sortKey="Tao, J" uniqKey="Tao J">J. Tao</name></author><author><name sortKey="Guo, D" uniqKey="Guo D">D. Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, C" uniqKey="Huang C">C. Huang</name></author><author><name sortKey="Lokugamage, K G" uniqKey="Lokugamage K">K.G. Lokugamage</name></author><author><name sortKey="Rozovics, J M" uniqKey="Rozovics J">J.M. Rozovics</name></author><author><name sortKey="Narayanan, K" uniqKey="Narayanan K">K. Narayanan</name></author><author><name sortKey="Semler, B L" uniqKey="Semler B">B.L. Semler</name></author><author><name sortKey="Makino, S" uniqKey="Makino S">S. Makino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lokugamage, K G" uniqKey="Lokugamage K">K.G. Lokugamage</name></author><author><name sortKey="Narayanan, K" uniqKey="Narayanan K">K. Narayanan</name></author><author><name sortKey="Nakagawa, K" uniqKey="Nakagawa K">K. Nakagawa</name></author><author><name sortKey="Terasaki, K" uniqKey="Terasaki K">K. Terasaki</name></author><author><name sortKey="Ramirez, S I" uniqKey="Ramirez S">S.I. Ramirez</name></author><author><name sortKey="Tseng, C T K" uniqKey="Tseng C">C.-T.K. Tseng</name></author><author><name sortKey="Ramirez, S I" uniqKey="Ramirez S">S.I. Ramirez</name></author><author><name sortKey="Tseng, C T" uniqKey="Tseng C">C.T. Tseng</name></author><author><name sortKey="Makino, S" uniqKey="Makino S">S. Makino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jauregui, A R" uniqKey="Jauregui A">A.R. Jauregui</name></author><author><name sortKey="Savalia, D" uniqKey="Savalia D">D. Savalia</name></author><author><name sortKey="Lowry, V K" uniqKey="Lowry V">V.K. Lowry</name></author><author><name sortKey="Farrell, C M" uniqKey="Farrell C">C.M. Farrell</name></author><author><name sortKey="Wathelet, M G" uniqKey="Wathelet M">M.G. Wathelet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mielech, A M" uniqKey="Mielech A">A.M. Mielech</name></author><author><name sortKey="Kilianski, A" uniqKey="Kilianski A">A. Kilianski</name></author><author><name sortKey="Baez Santos, Y M" uniqKey="Baez Santos Y">Y.M. Baez-Santos</name></author><author><name sortKey="Mesecar, A D" uniqKey="Mesecar A">A.D. Mesecar</name></author><author><name sortKey="Baker, S C" uniqKey="Baker S">S.C. Baker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Devaraj, S G" uniqKey="Devaraj S">S.G. Devaraj</name></author><author><name sortKey="Wang, N" uniqKey="Wang N">N. Wang</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z. Chen</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z. Chen</name></author><author><name sortKey="Tseng, M" uniqKey="Tseng M">M. Tseng</name></author><author><name sortKey="Barretto, N" uniqKey="Barretto N">N. Barretto</name></author><author><name sortKey="Lin, R" uniqKey="Lin R">R. Lin</name></author><author><name sortKey="Peters, C J" uniqKey="Peters C">C.J. Peters</name></author><author><name sortKey="Tseng, C T" uniqKey="Tseng C">C.T. Tseng</name></author><author><name sortKey="Baker, S C" uniqKey="Baker S">S.C. Baker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, X" uniqKey="Yang X">X. Yang</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X. Chen</name></author><author><name sortKey="Bian, G" uniqKey="Bian G">G. Bian</name></author><author><name sortKey="Tu, J" uniqKey="Tu J">J. Tu</name></author><author><name sortKey="Xing, Y" uniqKey="Xing Y">Y. Xing</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuri, T" uniqKey="Kuri T">T. Kuri</name></author><author><name sortKey="Eriksson, K K" uniqKey="Eriksson K">K.K. Eriksson</name></author><author><name sortKey="Putics, A" uniqKey="Putics A">A. Putics</name></author><author><name sortKey="Zust, R" uniqKey="Zust R">R. Züst</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E.J. Snijder</name></author><author><name sortKey="Davidson, A D" uniqKey="Davidson A">A.D. Davidson</name></author><author><name sortKey="Siddell, S G" uniqKey="Siddell S">S.G. Siddell</name></author><author><name sortKey="Thiel, V" uniqKey="Thiel V">V. Thiel</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author><author><name sortKey="Weber, F" uniqKey="Weber F">F. Weber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stevens, F J" uniqKey="Stevens F">F.J. Stevens</name></author><author><name sortKey="Argon, Y" uniqKey="Argon Y">Y. Argon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ron, D" uniqKey="Ron D">D. Ron</name></author><author><name sortKey="Walter, P" uniqKey="Walter P">P. Walter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fung, T S" uniqKey="Fung T">T.S. Fung</name></author><author><name sortKey="Liu, D X" uniqKey="Liu D">D.X. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Teske, B F" uniqKey="Teske B">B.F. Teske</name></author><author><name sortKey="Wek, S A" uniqKey="Wek S">S.A. Wek</name></author><author><name sortKey="Bunpo, P" uniqKey="Bunpo P">P. Bunpo</name></author><author><name sortKey="Cundiff, J K" uniqKey="Cundiff J">J.K. Cundiff</name></author><author><name sortKey="Mcclintick, J N" uniqKey="Mcclintick J">J.N. McClintick</name></author><author><name sortKey="Anthony, T G" uniqKey="Anthony T">T.G. Anthony</name></author><author><name sortKey="Wek, R C" uniqKey="Wek R">R.C. Wek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harding, H P" uniqKey="Harding H">H.P. Harding</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Bertolotti, A" uniqKey="Bertolotti A">A. Bertolotti</name></author><author><name sortKey="Zeng, H" uniqKey="Zeng H">H. Zeng</name></author><author><name sortKey="Ron, D" uniqKey="Ron D">D. Ron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harding, H P" uniqKey="Harding H">H.P. Harding</name></author><author><name sortKey="Novoa, I" uniqKey="Novoa I">I. Novoa</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Zeng, H" uniqKey="Zeng H">H. Zeng</name></author><author><name sortKey="Wek, R" uniqKey="Wek R">R. Wek</name></author><author><name sortKey="Schapira, M" uniqKey="Schapira M">M. Schapira</name></author><author><name sortKey="Ron, D" uniqKey="Ron D">D. Ron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oyadomari, S" uniqKey="Oyadomari S">S. Oyadomari</name></author><author><name sortKey="Mori, M" uniqKey="Mori M">M. Mori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fung, T S" uniqKey="Fung T">T.S. Fung</name></author><author><name sortKey="Huang, M" uniqKey="Huang M">M. Huang</name></author><author><name sortKey="Liu, D X" uniqKey="Liu D">D.X. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Minakshi, R" uniqKey="Minakshi R">R. Minakshi</name></author><author><name sortKey="Padhan, K" uniqKey="Padhan K">K. Padhan</name></author><author><name sortKey="Rani, M" uniqKey="Rani M">M. Rani</name></author><author><name sortKey="Khan, N" uniqKey="Khan N">N. Khan</name></author><author><name sortKey="Ahmad, F" uniqKey="Ahmad F">F. Ahmad</name></author><author><name sortKey="Jameel, S" uniqKey="Jameel S">S. Jameel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, C P" uniqKey="Chan C">C.-P. Chan</name></author><author><name sortKey="Siu, K L" uniqKey="Siu K">K.-L. Siu</name></author><author><name sortKey="Chin, K T" uniqKey="Chin K">K.-T. Chin</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.-Y. Yuen</name></author><author><name sortKey="Zheng, B" uniqKey="Zheng B">B. Zheng</name></author><author><name sortKey="Jin, D Y" uniqKey="Jin D">D.-Y. Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Siu, K L" uniqKey="Siu K">K.-L. Siu</name></author><author><name sortKey="Chan, C P" uniqKey="Chan C">C.-P. Chan</name></author><author><name sortKey="Kok, K H" uniqKey="Kok K">K.-H. Kok</name></author><author><name sortKey="C Y Woo, P" uniqKey="C Y Woo P">P. C-Y Woo</name></author><author><name sortKey="Jin, D Y" uniqKey="Jin D">D.-Y. Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liao, Y" uniqKey="Liao Y">Y. Liao</name></author><author><name sortKey="Fung, T S" uniqKey="Fung T">T.S. Fung</name></author><author><name sortKey="Huang, M" uniqKey="Huang M">M. Huang</name></author><author><name sortKey="Fang, S G" uniqKey="Fang S">S.G. Fang</name></author><author><name sortKey="Zhong, Y" uniqKey="Zhong Y">Y. Zhong</name></author><author><name sortKey="Liu, D X" uniqKey="Liu D">D.X. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Liao, Y" uniqKey="Liao Y">Y. Liao</name></author><author><name sortKey="Yap, P L" uniqKey="Yap P">P.L. Yap</name></author><author><name sortKey="Png, K J" uniqKey="Png K">K.J. Png</name></author><author><name sortKey="Tam, J P" uniqKey="Tam J">J.P. Tam</name></author><author><name sortKey="Liu, D X" uniqKey="Liu D">D.X. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hong, M" uniqKey="Hong M">M. Hong</name></author><author><name sortKey="Luo, S" uniqKey="Luo S">S. Luo</name></author><author><name sortKey="Baumeister, P" uniqKey="Baumeister P">P. Baumeister</name></author><author><name sortKey="Huang, J M" uniqKey="Huang J">J.-M. Huang</name></author><author><name sortKey="Gogia, R K" uniqKey="Gogia R">R.K. Gogia</name></author><author><name sortKey="Li, M" uniqKey="Li M">M. Li</name></author><author><name sortKey="Lee, A S" uniqKey="Lee A">A.S. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nadanaka, S" uniqKey="Nadanaka S">S. Nadanaka</name></author><author><name sortKey="Okada, T" uniqKey="Okada T">T. Okada</name></author><author><name sortKey="Yoshida, H" uniqKey="Yoshida H">H. Yoshida</name></author><author><name sortKey="Mori, K" uniqKey="Mori K">K. Mori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schroder, M" uniqKey="Schroder M">M. Schröder</name></author><author><name sortKey="Kaufman, R J" uniqKey="Kaufman R">R.J. Kaufman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshida, H" uniqKey="Yoshida H">H. Yoshida</name></author><author><name sortKey="Matsui, T" uniqKey="Matsui T">T. Matsui</name></author><author><name sortKey="Yamamoto, A" uniqKey="Yamamoto A">A. Yamamoto</name></author><author><name sortKey="Okada, T" uniqKey="Okada T">T. Okada</name></author><author><name sortKey="Mori, K" uniqKey="Mori K">K. Mori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sung, S C" uniqKey="Sung S">S.-C. Sung</name></author><author><name sortKey="Chao, C Y" uniqKey="Chao C">C.-Y. Chao</name></author><author><name sortKey="Jeng, K S" uniqKey="Jeng K">K.-S. Jeng</name></author><author><name sortKey="Yang, J Y" uniqKey="Yang J">J.-Y. Yang</name></author><author><name sortKey="Lai, M M C" uniqKey="Lai M">M.M.C. Lai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oostra, M" uniqKey="Oostra M">M. Oostra</name></author><author><name sortKey="De Haan, C A M" uniqKey="De Haan C">C.A.M. de Haan</name></author><author><name sortKey="Rottier, P J M" uniqKey="Rottier P">P.J.M. Rottier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Szegezdi, E" uniqKey="Szegezdi E">E. Szegezdi</name></author><author><name sortKey="Logue, S E" uniqKey="Logue S">S.E. Logue</name></author><author><name sortKey="Gorman, A M" uniqKey="Gorman A">A.M. Gorman</name></author><author><name sortKey="Samali, A" uniqKey="Samali A">A. Samali</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mori, K" uniqKey="Mori K">K. Mori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Credle, J J" uniqKey="Credle J">J.J. Credle</name></author><author><name sortKey="Finer Moore, J S" uniqKey="Finer Moore J">J.S. Finer-Moore</name></author><author><name sortKey="Papa, F R" uniqKey="Papa F">F.R. Papa</name></author><author><name sortKey="Stroud, R M" uniqKey="Stroud R">R.M. Stroud</name></author><author><name sortKey="Walter, P" uniqKey="Walter P">P. Walter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gardner, B M" uniqKey="Gardner B">B.M. Gardner</name></author><author><name sortKey="Walter, P" uniqKey="Walter P">P. Walter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prischi, F" uniqKey="Prischi F">F. Prischi</name></author><author><name sortKey="Nowak, P R" uniqKey="Nowak P">P.R. Nowak</name></author><author><name sortKey="Carrara, M" uniqKey="Carrara M">M. Carrara</name></author><author><name sortKey="Ali, M M U" uniqKey="Ali M">M.M.U. Ali</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, B" uniqKey="Gao B">B. Gao</name></author><author><name sortKey="Lee, S M" uniqKey="Lee S">S.-M. Lee</name></author><author><name sortKey="Chen, A" uniqKey="Chen A">A. Chen</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author><author><name sortKey="Zhang, D D" uniqKey="Zhang D">D.D. Zhang</name></author><author><name sortKey="Kannan, K" uniqKey="Kannan K">K. Kannan</name></author><author><name sortKey="Ortmann, R A" uniqKey="Ortmann R">R.A. Ortmann</name></author><author><name sortKey="Fang, D" uniqKey="Fang D">D. Fang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshida, H" uniqKey="Yoshida H">H. Yoshida</name></author><author><name sortKey="Oku, M" uniqKey="Oku M">M. Oku</name></author><author><name sortKey="Suzuki, M" uniqKey="Suzuki M">M. Suzuki</name></author><author><name sortKey="Mori, K" uniqKey="Mori K">K. Mori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tam, A B" uniqKey="Tam A">A.B. Tam</name></author><author><name sortKey="Koong, A C" uniqKey="Koong A">A.C. Koong</name></author><author><name sortKey="Niwa, M" uniqKey="Niwa M">M. Niwa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walter, F" uniqKey="Walter F">F. Walter</name></author><author><name sortKey="Schmid, J" uniqKey="Schmid J">J. Schmid</name></author><author><name sortKey="Dussmann, H" uniqKey="Dussmann H">H. Dussmann</name></author><author><name sortKey="Concannon, C G" uniqKey="Concannon C">C.G. Concannon</name></author><author><name sortKey="Prehn, J H M" uniqKey="Prehn J">J.H.M. Prehn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Urano, F" uniqKey="Urano F">F. Urano</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Bertolotti, A" uniqKey="Bertolotti A">A. Bertolotti</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Chung, P" uniqKey="Chung P">P. Chung</name></author><author><name sortKey="Harding, H P" uniqKey="Harding H">H.P. Harding</name></author><author><name sortKey="Ron, D" uniqKey="Ron D">D. Ron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Versteeg, G A" uniqKey="Versteeg G">G.A. Versteeg</name></author><author><name sortKey="Van De Nes, P S" uniqKey="Van De Nes P">P.S. van de Nes</name></author><author><name sortKey="Bredenbeek, P J" uniqKey="Bredenbeek P">P.J. Bredenbeek</name></author><author><name sortKey="Spaan, W J M" uniqKey="Spaan W">W.J.M. Spaan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fung, T S" uniqKey="Fung T">T.S. Fung</name></author><author><name sortKey="Liao, Y" uniqKey="Liao Y">Y. Liao</name></author><author><name sortKey="Liu, D X" uniqKey="Liu D">D.X. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dhillon, A S" uniqKey="Dhillon A">A.S. Dhillon</name></author><author><name sortKey="Hagan, S" uniqKey="Hagan S">S. Hagan</name></author><author><name sortKey="Rath, O" uniqKey="Rath O">O. Rath</name></author><author><name sortKey="Kolch, W" uniqKey="Kolch W">W. Kolch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Davis, R J" uniqKey="Davis R">R.J. Davis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Panteva, M" uniqKey="Panteva M">M. Panteva</name></author><author><name sortKey="Korkaya, H" uniqKey="Korkaya H">H. Korkaya</name></author><author><name sortKey="Jameel, S" uniqKey="Jameel S">S. Jameel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arthur, J S C" uniqKey="Arthur J">J.S.C. Arthur</name></author><author><name sortKey="Ley, S C" uniqKey="Ley S">S.C. Ley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Keshet, Y" uniqKey="Keshet Y">Y. Keshet</name></author><author><name sortKey="Seger, R" uniqKey="Seger R">R. Seger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mizutani, T" uniqKey="Mizutani T">T. Mizutani</name></author><author><name sortKey="Fukushi, S" uniqKey="Fukushi S">S. Fukushi</name></author><author><name sortKey="Murakami, M" uniqKey="Murakami M">M. Murakami</name></author><author><name sortKey="Hirano, T" uniqKey="Hirano T">T. Hirano</name></author><author><name sortKey="Saijo, M" uniqKey="Saijo M">M. Saijo</name></author><author><name sortKey="Kurane, I" uniqKey="Kurane I">I. Kurane</name></author><author><name sortKey="Morikawa, S" uniqKey="Morikawa S">S. Morikawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mizutani, T" uniqKey="Mizutani T">T. Mizutani</name></author><author><name sortKey="Fukushi, S" uniqKey="Fukushi S">S. Fukushi</name></author><author><name sortKey="Saijo, M" uniqKey="Saijo M">M. Saijo</name></author><author><name sortKey="Kurane, I" uniqKey="Kurane I">I. Kurane</name></author><author><name sortKey="Morikawa, S" uniqKey="Morikawa S">S. Morikawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, I Y" uniqKey="Chen I">I.Y. Chen</name></author><author><name sortKey="Chang, S C" uniqKey="Chang S">S.C. Chang</name></author><author><name sortKey="Wu, H Y" uniqKey="Wu H">H.-Y. Wu</name></author><author><name sortKey="Yu, T C" uniqKey="Yu T">T.-C. Yu</name></author><author><name sortKey="Wei, W C" uniqKey="Wei W">W.-C. Wei</name></author><author><name sortKey="Lin, S" uniqKey="Lin S">S. Lin</name></author><author><name sortKey="Chien, C L" uniqKey="Chien C">C.L. Chien</name></author><author><name sortKey="Chang, M F" uniqKey="Chang M">M.F. Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mizutani, T" uniqKey="Mizutani T">T. Mizutani</name></author><author><name sortKey="Fukushi, S" uniqKey="Fukushi S">S. Fukushi</name></author><author><name sortKey="Saijo, M" uniqKey="Saijo M">M. Saijo</name></author><author><name sortKey="Kurane, I" uniqKey="Kurane I">I. Kurane</name></author><author><name sortKey="Morikawa, S" uniqKey="Morikawa S">S. Morikawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yao, Y" uniqKey="Yao Y">Y. Yao</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Wu, J" uniqKey="Wu J">J. Wu</name></author><author><name sortKey="Germann, U A" uniqKey="Germann U">U.A. Germann</name></author><author><name sortKey="Su, M S" uniqKey="Su M">M.S. Su</name></author><author><name sortKey="Kuida, K" uniqKey="Kuida K">K. Kuida</name></author><author><name sortKey="Boucher, D M" uniqKey="Boucher D">D.M. Boucher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, Y T C" uniqKey="Yu Y">Y.T.-C. Yu</name></author><author><name sortKey="Chien, S C" uniqKey="Chien S">S.-C. Chien</name></author><author><name sortKey="Chen, I Y" uniqKey="Chen I">I.Y. Chen</name></author><author><name sortKey="Lai, C T" uniqKey="Lai C">C.-T. Lai</name></author><author><name sortKey="Tsay, Y G" uniqKey="Tsay Y">Y.-G. Tsay</name></author><author><name sortKey="Chang, S C" uniqKey="Chang S">S.C. Chang</name></author><author><name sortKey="Chang, M F" uniqKey="Chang M">M.F. Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kumar, N" uniqKey="Kumar N">N. Kumar</name></author><author><name sortKey="Robidoux, J" uniqKey="Robidoux J">J. Robidoux</name></author><author><name sortKey="Daniel, K W" uniqKey="Daniel K">K.W. Daniel</name></author><author><name sortKey="Guzman, G" uniqKey="Guzman G">G. Guzman</name></author><author><name sortKey="Floering, L M" uniqKey="Floering L">L.M. Floering</name></author><author><name sortKey="Collins, S" uniqKey="Collins S">S. Collins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, Y J" uniqKey="Chang Y">Y.-J. Chang</name></author><author><name sortKey="Liu, C Y Y" uniqKey="Liu C">C.Y.-Y. Liu</name></author><author><name sortKey="Chiang, B L" uniqKey="Chiang B">B.-L. Chiang</name></author><author><name sortKey="Chao, Y C" uniqKey="Chao Y">Y.-C. Chao</name></author><author><name sortKey="Chen, C C" uniqKey="Chen C">C.-C. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, S W" uniqKey="Li S">S.-W. Li</name></author><author><name sortKey="Lai, C C" uniqKey="Lai C">C.-C. Lai</name></author><author><name sortKey="Ping, J F" uniqKey="Ping J">J.-F. Ping</name></author><author><name sortKey="Tsai, F J" uniqKey="Tsai F">F.-J. Tsai</name></author><author><name sortKey="Wan, L" uniqKey="Wan L">L. Wan</name></author><author><name sortKey="Lin, Y J" uniqKey="Lin Y">Y.-J. Lin</name></author><author><name sortKey="Kung, S H" uniqKey="Kung S">S.H. Kung</name></author><author><name sortKey="Lin, C W" uniqKey="Lin C">C.W. Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Varshney, B" uniqKey="Varshney B">B. Varshney</name></author><author><name sortKey="Lal, S" uniqKey="Lal S">S. Lal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kindrachuk, J" uniqKey="Kindrachuk J">J. Kindrachuk</name></author><author><name sortKey="Ork, B" uniqKey="Ork B">B. Ork</name></author><author><name sortKey="Hart, B J" uniqKey="Hart B">B.J. Hart</name></author><author><name sortKey="Mazur, S" uniqKey="Mazur S">S. Mazur</name></author><author><name sortKey="Holbrook, M R" uniqKey="Holbrook M">M.R. Holbrook</name></author><author><name sortKey="Frieman, M B" uniqKey="Frieman M">M.B. Frieman</name></author><author><name sortKey="Traynor, D" uniqKey="Traynor D">D. Traynor</name></author><author><name sortKey="Johnson, R F" uniqKey="Johnson R">R.F. Johnson</name></author><author><name sortKey="Dyall, J" uniqKey="Dyall J">J. Dyall</name></author><author><name sortKey="Kuhn, J H" uniqKey="Kuhn J">J.H. Kuhn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kono, M" uniqKey="Kono M">M. Kono</name></author><author><name sortKey="Tatsumi, K" uniqKey="Tatsumi K">K. Tatsumi</name></author><author><name sortKey="Imai, A M" uniqKey="Imai A">A.M. Imai</name></author><author><name sortKey="Saito, K" uniqKey="Saito K">K. Saito</name></author><author><name sortKey="Kuriyama, T" uniqKey="Kuriyama T">T. Kuriyama</name></author><author><name sortKey="Shirasawa, H" uniqKey="Shirasawa H">H. Shirasawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mizutani, T" uniqKey="Mizutani T">T. Mizutani</name></author><author><name sortKey="Fukushi, S" uniqKey="Fukushi S">S. Fukushi</name></author><author><name sortKey="Saijo, M" uniqKey="Saijo M">M. Saijo</name></author><author><name sortKey="Kurane, I" uniqKey="Kurane I">I. Kurane</name></author><author><name sortKey="Morikawa, S" uniqKey="Morikawa S">S. Morikawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kanzawa, N" uniqKey="Kanzawa N">N. Kanzawa</name></author><author><name sortKey="Nishigaki, K" uniqKey="Nishigaki K">K. Nishigaki</name></author><author><name sortKey="Hayashi, T" uniqKey="Hayashi T">T. Hayashi</name></author><author><name sortKey="Ishii, Y" uniqKey="Ishii Y">Y. Ishii</name></author><author><name sortKey="Furukawa, S" uniqKey="Furukawa S">S. Furukawa</name></author><author><name sortKey="Niiro, A" uniqKey="Niiro A">A. Niiro</name></author><author><name sortKey="Yasui, F" uniqKey="Yasui F">F. Yasui</name></author><author><name sortKey="Kohara, M" uniqKey="Kohara M">M. Kohara</name></author><author><name sortKey="Morita, K" uniqKey="Morita K">K. Morita</name></author><author><name sortKey="Matsushima, K" uniqKey="Matsushima K">K. Matsushima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, M" uniqKey="Liu M">M. Liu</name></author><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y. Yang</name></author><author><name sortKey="Gu, C" uniqKey="Gu C">C. Gu</name></author><author><name sortKey="Yue, Y" uniqKey="Yue Y">Y. Yue</name></author><author><name sortKey="Wu, K K" uniqKey="Wu K">K.K. Wu</name></author><author><name sortKey="Wu, J" uniqKey="Wu J">J. Wu</name></author><author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y. Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fung, T S" uniqKey="Fung T">T.S. Fung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kopecky Bromberg, S A" uniqKey="Kopecky Bromberg S">S.A. Kopecky-Bromberg</name></author><author><name sortKey="Martinez Sobrido, L" uniqKey="Martinez Sobrido L">L. Martinez-Sobrido</name></author><author><name sortKey="Palese, P" uniqKey="Palese P">P. Palese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, Y J" uniqKey="Tan Y">Y.-J. Tan</name></author><author><name sortKey="Teng, E" uniqKey="Teng E">E. Teng</name></author><author><name sortKey="Shen, S" uniqKey="Shen S">S. Shen</name></author><author><name sortKey="Tan, T H P" uniqKey="Tan T">T.H.P. Tan</name></author><author><name sortKey="Goh, P Y" uniqKey="Goh P">P.-Y. Goh</name></author><author><name sortKey="Fielding, B C" uniqKey="Fielding B">B.C. Fielding</name></author><author><name sortKey="Ooi, E E" uniqKey="Ooi E">E.E. Ooi</name></author><author><name sortKey="Tan, H C" uniqKey="Tan H">H.C. Tan</name></author><author><name sortKey="Lim, S G" uniqKey="Lim S">S.G. Lim</name></author><author><name sortKey="Hong, W" uniqKey="Hong W">W. Hong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jimenez Guarde O, J M" uniqKey="Jimenez Guarde O J">J.M. Jimenez-Guardeño</name></author><author><name sortKey="Nieto Torres, J L" uniqKey="Nieto Torres J">J.L. Nieto-Torres</name></author><author><name sortKey="Dediego, M L" uniqKey="Dediego M">M.L. DeDiego</name></author><author><name sortKey="Regla Nava, J A" uniqKey="Regla Nava J">J.A. Regla-Nava</name></author><author><name sortKey="Fernandez Delgado, R" uniqKey="Fernandez Delgado R">R. Fernandez-Delgado</name></author><author><name sortKey="Casta O Rodriguez, C" uniqKey="Casta O Rodriguez C">C. Castaño-Rodriguez</name></author><author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L. Enjuanes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, C H" uniqKey="Lee C">C.-H. Lee</name></author><author><name sortKey="Chen, R F" uniqKey="Chen R">R.-F. Chen</name></author><author><name sortKey="Liu, J W" uniqKey="Liu J">J.-W. Liu</name></author><author><name sortKey="Yeh, W T" uniqKey="Yeh W">W.-T. Yeh</name></author><author><name sortKey="Chang, J C" uniqKey="Chang J">J.-C. Chang</name></author><author><name sortKey="Liu, P M" uniqKey="Liu P">P.-M. Liu</name></author><author><name sortKey="Eng, H L" uniqKey="Eng H">H.L. Eng</name></author><author><name sortKey="Lin, M C" uniqKey="Lin M">M.C. Lin</name></author><author><name sortKey="Yang, K D" uniqKey="Yang K">K.D. Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Santoro, M" uniqKey="Santoro M">M. Santoro</name></author><author><name sortKey="Rossi, A" uniqKey="Rossi A">A. Rossi</name></author><author><name sortKey="Amici, C" uniqKey="Amici C">C. Amici</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoesel, B" uniqKey="Hoesel B">B. Hoesel</name></author><author><name sortKey="Schmid, J A" uniqKey="Schmid J">J.A. Schmid</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hiscott, J" uniqKey="Hiscott J">J. Hiscott</name></author><author><name sortKey="Kwon, H" uniqKey="Kwon H">H. Kwon</name></author><author><name sortKey="Genin, P" uniqKey="Genin P">P. Génin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, S C" uniqKey="Sun S">S.-C. Sun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Diego, M L" uniqKey="De Diego M">M.L. De Diego</name></author><author><name sortKey="Nieto Torres, J L" uniqKey="Nieto Torres J">J.L. Nieto-Torres</name></author><author><name sortKey="Regla Nava, J A" uniqKey="Regla Nava J">J.A. Regla-Nava</name></author><author><name sortKey="Jimenez Guarde O, J M" uniqKey="Jimenez Guarde O J">J.M. Jimenez-Guardeño</name></author><author><name sortKey="Fernandez Delgado, R" uniqKey="Fernandez Delgado R">R. Fernandez-Delgado</name></author><author><name sortKey="Fett, C" uniqKey="Fett C">C. Fett</name></author><author><name sortKey="Casta O Rodriguez, C" uniqKey="Casta O Rodriguez C">C. Castaño-Rodriguez</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author><author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L. Enjuanes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dosch, S F" uniqKey="Dosch S">S.F. Dosch</name></author><author><name sortKey="Mahajan, S D" uniqKey="Mahajan S">S.D. Mahajan</name></author><author><name sortKey="Collins, A R" uniqKey="Collins A">A.R. Collins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liao, Q J" uniqKey="Liao Q">Q.-J. Liao</name></author><author><name sortKey="Ye, L B" uniqKey="Ye L">L.-B. Ye</name></author><author><name sortKey="Timani, K A" uniqKey="Timani K">K.A. Timani</name></author><author><name sortKey="Zeng, Y C" uniqKey="Zeng Y">Y.-C. Zeng</name></author><author><name sortKey="She, Y L" uniqKey="She Y">Y.-L. She</name></author><author><name sortKey="Ye, L" uniqKey="Ye L">L. Ye</name></author><author><name sortKey="Wu, Z H" uniqKey="Wu Z">Z.H. Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, R" uniqKey="He R">R. He</name></author><author><name sortKey="Leeson, A" uniqKey="Leeson A">A. Leeson</name></author><author><name sortKey="Andonov, A" uniqKey="Andonov A">A. Andonov</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Bastien, N" uniqKey="Bastien N">N. Bastien</name></author><author><name sortKey="Cao, J" uniqKey="Cao J">J. Cao</name></author><author><name sortKey="Osiowy, C" uniqKey="Osiowy C">C. Osiowy</name></author><author><name sortKey="Dobie, F" uniqKey="Dobie F">F. Dobie</name></author><author><name sortKey="Cutts, T" uniqKey="Cutts T">T. Cutts</name></author><author><name sortKey="Ballantine, M" uniqKey="Ballantine M">M. Ballantine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fang, X" uniqKey="Fang X">X. Fang</name></author><author><name sortKey="Gao, J" uniqKey="Gao J">J. Gao</name></author><author><name sortKey="Zheng, H" uniqKey="Zheng H">H. Zheng</name></author><author><name sortKey="Li, B" uniqKey="Li B">B. Li</name></author><author><name sortKey="Kong, L" uniqKey="Kong L">L. Kong</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Wang, W" uniqKey="Wang W">W. Wang</name></author><author><name sortKey="Zeng, Y" uniqKey="Zeng Y">Y. Zeng</name></author><author><name sortKey="Ye, L" uniqKey="Ye L">L. Ye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, F W" uniqKey="Lai F">F.W. Lai</name></author><author><name sortKey="Stephenson, K B" uniqKey="Stephenson K">K.B. Stephenson</name></author><author><name sortKey="Mahony, J" uniqKey="Mahony J">J. Mahony</name></author><author><name sortKey="Lichty, B D" uniqKey="Lichty B">B.D. Lichty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Law, A H Y" uniqKey="Law A">A.H.Y. Law</name></author><author><name sortKey="Lee, D C W" uniqKey="Lee D">D.C.W. Lee</name></author><author><name sortKey="Cheung, B K W" uniqKey="Cheung B">B.K.W. Cheung</name></author><author><name sortKey="Yim, H C H" uniqKey="Yim H">H.C.H. Yim</name></author><author><name sortKey="Lau, A S Y" uniqKey="Lau A">A.S.Y. Lau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frieman, M" uniqKey="Frieman M">M. Frieman</name></author><author><name sortKey="Ratia, K" uniqKey="Ratia K">K. Ratia</name></author><author><name sortKey="Johnston, R E" uniqKey="Johnston R">R.E. Johnston</name></author><author><name sortKey="Mesecar, A D" uniqKey="Mesecar A">A.D. Mesecar</name></author><author><name sortKey="Baric, R S" uniqKey="Baric R">R.S. Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ratia, K" uniqKey="Ratia K">K. Ratia</name></author><author><name sortKey="Kilianski, A" uniqKey="Kilianski A">A. Kilianski</name></author><author><name sortKey="Baez Santos, Y M" uniqKey="Baez Santos Y">Y.M. Baez-Santos</name></author><author><name sortKey="Baker, S C" uniqKey="Baker S">S.C. Baker</name></author><author><name sortKey="Mesecar, A" uniqKey="Mesecar A">A. Mesecar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matthews, K L" uniqKey="Matthews K">K.L. Matthews</name></author><author><name sortKey="Coleman, C M" uniqKey="Coleman C">C.M. Coleman</name></author><author><name sortKey="Van Der Meer, Y" uniqKey="Van Der Meer Y">Y. van der Meer</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E.J. Snijder</name></author><author><name sortKey="Frieman, M B" uniqKey="Frieman M">M.B. Frieman</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Diseases</journal-id><journal-id journal-id-type="iso-abbrev">Diseases</journal-id><journal-id journal-id-type="publisher-id">diseases</journal-id><journal-title-group><journal-title>Diseases</journal-title></journal-title-group><issn pub-type="epub">2079-9721</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28933406</article-id><article-id pub-id-type="pmc">5456285</article-id><article-id pub-id-type="doi">10.3390/diseases4030026</article-id><article-id pub-id-type="publisher-id">diseases-04-00026</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Human Coronaviruses: A Review of Virus–Host Interactions</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lim</surname><given-names>Yvonne Xinyi</given-names></name></contrib><contrib contrib-type="author"><name><surname>Ng</surname><given-names>Yan Ling</given-names></name></contrib><contrib contrib-type="author"><name><surname>Tam</surname><given-names>James P.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Ding Xiang</given-names></name><xref rid="c1-diseases-04-00026" ref-type="corresp">*</xref></contrib></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Battino</surname><given-names>Maurizio</given-names></name><role>Academic Editor</role></contrib></contrib-group><aff id="af1-diseases-04-00026">School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore;<email>YVON0016@e.ntu.edu.sg</email> (Y.X.L.);<email>S150004@e.ntu.edu.sg</email> (Y.L.N.);<email>JPTAM@ntu.edu.sg</email> (J.P.T.)</aff><author-notes><corresp id="c1-diseases-04-00026"><label>*</label>Correspondence: <email>dxliu0001@163.com</email>; Tel.: +65-6316-2861</corresp></author-notes><pub-date pub-type="epub"><day>25</day><month>7</month><year>2016</year></pub-date><pub-date pub-type="collection"><month>9</month><year>2016</year></pub-date><volume>4</volume><issue>3</issue><elocation-id>26</elocation-id><history><date date-type="received"><day>08</day><month>6</month><year>2016</year></date><date date-type="accepted"><day>18</day><month>7</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 by the authors.</copyright-statement><copyright-year>2016</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs.</p></abstract><kwd-group><kwd>human coronavirus</kwd><kwd>virus–host interactions</kwd><kwd>apoptosis</kwd><kwd>innate immunity</kwd><kwd>ER stress</kwd><kwd>MAPK</kwd><kwd>NF-κB</kwd></kwd-group></article-meta></front><body><sec id="sec1-diseases-04-00026"><title>1. Introduction</title><p>Human coronaviruses (HCoVs) represent a major group of coronaviruses (CoVs) associated with multiple respiratory diseases of varying severity, including common cold, pneumonia and bronchilitis [<xref rid="B1-diseases-04-00026" ref-type="bibr">1</xref>]. Today, HCoVs are recognised as one of the most rapidly evolving viruses owing to its high genomic nucleotide substitution rates and recombination [<xref rid="B2-diseases-04-00026" ref-type="bibr">2</xref>]. In recent years, evolution of HCoVs has also been expedited by factors such as urbanization and poultry farming. These have permitted the frequent mixing of species and facilitated the crossing of species barrier and genomic recombination of these viruses [<xref rid="B3-diseases-04-00026" ref-type="bibr">3</xref>]. To date, six known HCoVs have been identified, namely HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV); of which, four HCoVs (HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1) are globally circulated in the human population and contribute to approximately one-third of common cold infections in humans [<xref rid="B4-diseases-04-00026" ref-type="bibr">4</xref>]. In severe cases, these four HCoVs can cause life-threatening pneumonia and bronchiolitis especially in elderly, children and immunocompromised patients [<xref rid="B1-diseases-04-00026" ref-type="bibr">1</xref>,<xref rid="B5-diseases-04-00026" ref-type="bibr">5</xref>,<xref rid="B6-diseases-04-00026" ref-type="bibr">6</xref>]. Besides respiratory illnesses, they may also cause enteric and neurological diseases [<xref rid="B7-diseases-04-00026" ref-type="bibr">7</xref>,<xref rid="B8-diseases-04-00026" ref-type="bibr">8</xref>,<xref rid="B9-diseases-04-00026" ref-type="bibr">9</xref>,<xref rid="B10-diseases-04-00026" ref-type="bibr">10</xref>,<xref rid="B11-diseases-04-00026" ref-type="bibr">11</xref>].</p><p>SARS-CoV first emerged in 2002–2003 in Guangdong, China as an atypical pneumonia marked by fever, headache and subsequent onset of respiratory symptoms such as cough and pneumonia, which may later develop into life-threatening respiratory failure and acute respiratory distress syndrome [<xref rid="B12-diseases-04-00026" ref-type="bibr">12</xref>]. Being highly transmissible among humans, it quickly spread across 29 countries, infecting more than 8000 individuals with a mortality rate of about 10% [<xref rid="B13-diseases-04-00026" ref-type="bibr">13</xref>,<xref rid="B14-diseases-04-00026" ref-type="bibr">14</xref>]. Originally, palm civets were thought to be the natural reservoir for the virus [<xref rid="B15-diseases-04-00026" ref-type="bibr">15</xref>]. However, subsequent phylogenetic studies pointed to the bat origin of SARS-CoV based on sequences of SARS-like virus found in bats [<xref rid="B16-diseases-04-00026" ref-type="bibr">16</xref>]. The MERS-CoV epidemic surfaced in Saudi Arabia in 2012 with similar clinical symptoms as SARS-CoV but with a much higher mortality rate of about 35% [<xref rid="B17-diseases-04-00026" ref-type="bibr">17</xref>]. Unlike SARS-CoV, which exhibits super-spreader events, transmission of MERS-CoV is geographically limited [<xref rid="B12-diseases-04-00026" ref-type="bibr">12</xref>]. In fact, reported cases of MERS-CoV often stem from outbreaks within the Middle Eastern countries or recent travel to the region [<xref rid="B18-diseases-04-00026" ref-type="bibr">18</xref>,<xref rid="B19-diseases-04-00026" ref-type="bibr">19</xref>].</p><sec><title>Taxonomy, Genomic Structure and Morphology</title><p>CoVs are a group of large enveloped RNA viruses under the Coronaviridae family. Together with Artierivirdae and Roniviridae, Coronaviridae is classified under the Nidovirale order [<xref rid="B20-diseases-04-00026" ref-type="bibr">20</xref>]. As proposed by the International Committee for Taxonomy of Viruses, CoVs are further categorized into four main genera, <italic>Alpha-</italic>, <italic>Beta-</italic>, <italic>Gamma</italic>- and <italic>Deltacoronaviruses</italic> based on sequence comparisons of entire viral genomes [<xref rid="B21-diseases-04-00026" ref-type="bibr">21</xref>,<xref rid="B22-diseases-04-00026" ref-type="bibr">22</xref>]. These CoVs can infect a wide variety of hosts, including avian, swine and humans. HCoVs are identified to be either in the <italic>Alpha-</italic> or <italic>Betacoronavirus</italic> genera, including <italic>Alphacoronaviruses</italic>, HCoV-229E and HCoV-NL63, and <italic>Betacoronaviruses</italic>, HCoV-HKU1, SARS-CoV, MERS-CoV and HCoV-OC43 (<xref ref-type="table" rid="diseases-04-00026-t001">Table 1</xref>).</p><p>Under the electron microscope, the CoV virions appear to be roughly spherical or moderately pleomorphic, with distinct “club-like” projections formed by the spike (S) protein [<xref rid="B23-diseases-04-00026" ref-type="bibr">23</xref>,<xref rid="B24-diseases-04-00026" ref-type="bibr">24</xref>]. Within the virion interior lies a helically symmetrical nucleocapsid that encloses a single-stranded and positive sense RNA viral genome of an extraordinarily large size of about 26 to 32 kilobases [<xref rid="B20-diseases-04-00026" ref-type="bibr">20</xref>]. The positive sense viral genomic RNA acts as a messenger RNA (mRNA), comprising a 5′ terminal cap structure and a 3′ poly A tail. This genomic RNA acts in three capacities during the viral life cycle: (1) as an initial RNA of the infectious cycle; (2) as a template for replication and transcription; and (3) as a substrate for packaging into the progeny virus. The replicase-transcriptase is the only protein translated from the genome, while the viral products of all downstream open reading frames are derived from subgenomic mRNAs. In all CoVs, the replicase gene makes up approximately 5′ two-thirds of the genome and is comprised of two overlapping open reading frames (ORFs), ORF1a and ORF1b, which encodes 16 non-structural proteins. The final one-third of the CoV genomic RNA encodes CoV canonical set of four structural protein genes, in the order of spike (S), envelope (E), membrane (M) and nucleocapsid (N). In addition, several accessory ORFs are also interspersed along the structural protein genes and the number and location varies among CoV species [<xref rid="B25-diseases-04-00026" ref-type="bibr">25</xref>] (<xref ref-type="fig" rid="diseases-04-00026-f001">Figure 1</xref>).</p></sec></sec><sec id="sec2-diseases-04-00026"><title>2. Involvement of Host Factors in Viral Replication and Pathogenesis</title><p>As intracellular obligate parasites, HCoVs exploit the host cell machinery for their own replication and spread. Since virus–host interactions form the basis of diseases, knowledge about their interplay is of great research interest. Here, we describe what is currently known of the cell’s contribution in CoV infection cycle: attachment; entry into the host cell; translation of the replicase-transcriptase; replication of genome and transcription of mRNAs; and assembly and budding of newly packaged virions (<xref ref-type="fig" rid="diseases-04-00026-f002">Figure 2</xref>). </p><sec id="sec2dot1-diseases-04-00026"><title>2.1. Coronavirus Attachment and Entry</title><p>CoV infection is initiated by the attachment to specific host cellular receptors via the spike (S) protein. The host receptor is a major determinant of pathogenicity, tissue tropism and host range of the virus. The S protein comprises of two domains: S1 and S2. The interaction between the S1 domain and its cognate receptor triggers a conformational change in the S protein, which then promotes membrane fusion between the viral and cell membrane through the S2 domain. Today, the main host cell receptors utilised by all HCoVs are known: aminopeptidase N by HCoV-229E [<xref rid="B26-diseases-04-00026" ref-type="bibr">26</xref>], angiotensin-converting enzyme 2 (ACE2) by SARS-CoV [<xref rid="B27-diseases-04-00026" ref-type="bibr">27</xref>] and HCoV-NL63 [<xref rid="B28-diseases-04-00026" ref-type="bibr">28</xref>,<xref rid="B29-diseases-04-00026" ref-type="bibr">29</xref>], dipeptidyl peptidase 4 (DPP4) by MERS-CoV [<xref rid="B30-diseases-04-00026" ref-type="bibr">30</xref>] and 9-<italic>O</italic>-acetylated sialic acid by HCoV-OC43 and HCoV-HKU1 [<xref rid="B31-diseases-04-00026" ref-type="bibr">31</xref>,<xref rid="B32-diseases-04-00026" ref-type="bibr">32</xref>].</p><p>Apart from the conventional endosomal route of entry, some CoVs may also gain entry into the cell via the non-endosomal pathway, or a combination of both. The low pH in the cellular environment and endosomal cysteine protease cathepsins may help to facilitate membrane fusion and endosomal CoV cell entry [<xref rid="B33-diseases-04-00026" ref-type="bibr">33</xref>]. Recent evidence has supported the role of cathepsin L in SARS-CoV and MERS-CoV entry [<xref rid="B34-diseases-04-00026" ref-type="bibr">34</xref>,<xref rid="B35-diseases-04-00026" ref-type="bibr">35</xref>,<xref rid="B36-diseases-04-00026" ref-type="bibr">36</xref>]. Other host proteases, such as transmembrane protease serine 2 (TMPRSS2) and airway trypsin-like protease TMPRSS11D, could also perform S1/S2 cleavage to activate the S protein for non-endosomal virus entry at the cell plasma membrane during HCoV-229E and SARS-CoV infection [<xref rid="B37-diseases-04-00026" ref-type="bibr">37</xref>,<xref rid="B38-diseases-04-00026" ref-type="bibr">38</xref>]. In addition, MERS-CoV is also activated by furin, a serine endopeptidase that has been implicated in the cell entry of other RNA viruses and S1/S2 cleavage during viral egress [<xref rid="B39-diseases-04-00026" ref-type="bibr">39</xref>].</p><p>Many host cells also utilise its own factors to restrict viral entry. Using cell culture system and pseudotype virus, many groups have identified a family of interferon inducible transmembrane proteins (IFITM), which could inhibit global circulating HCoV-229E and HCoV-NL63 S protein mediated entry, and also the highly pathogenic SARS-CoV and MERS-CoV [<xref rid="B12-diseases-04-00026" ref-type="bibr">12</xref>,<xref rid="B40-diseases-04-00026" ref-type="bibr">40</xref>]. While the IFITM mode of action remains elusive, cell-to-cell fusion assays performed by some research groups suggest that IFITM3 blocks the enveloped virus entry by preventing fusion of the viral envelope with the plasma membrane or endosomal membranes through modulating the host membrane fluidity [<xref rid="B41-diseases-04-00026" ref-type="bibr">41</xref>].</p></sec><sec id="sec2dot2-diseases-04-00026"><title>2.2. Coronavirus Replication</title><p>Following the release and uncoating of viral nucleocapsid to the cytoplasm, CoV replication begins with the translation of ORF 1a and 1b into polyproteins pp1a (4382 amino acids) and pp1ab (7073 amino acids). Here, the downstream ORF1b is translated through ribosomal frameshifting mechanism, in which a translating ribosome shifts one nucleotide in the −1 direction, from the ORF1a reading frame into ORF1b reading frame. This repositioning is enabled by two RNA elements—a 5′-UUUAAAC-3′ heptanucleotide slippery sequence and RNA pseudoknot structure. Subsequently, polyproteins pp1a and pp1ab are cleaved into at least 15 nsp, which assemble and form the replication-transcription complex. With the assembly of the replicase-polymerase, the full-length positive strand of genomic RNA is transcribed to form a full-length negative-strand template for the synthesis of new genomic RNAs and overlapping subgenomic negative-strand templates. These subgenomic mRNAs are then transcribed and translated to produce the structural and accessory proteins. Several heterologous nuclear ribonucleoprotein (hnRNA) family members (hnRNPA1, PTB, SYN-CRYP) have been found to be essential for efficient RNA replication [<xref rid="B42-diseases-04-00026" ref-type="bibr">42</xref>]. Other RNA-binding proteins have also been suggested to play a role in CoV replication, such as m-aconitase and poly-A-binding protein (PABP), DDX1, PCBP1/2 and zinc finger CCHC-type and RNA-binding motif 1 (MADP1) [<xref rid="B43-diseases-04-00026" ref-type="bibr">43</xref>,<xref rid="B44-diseases-04-00026" ref-type="bibr">44</xref>,<xref rid="B45-diseases-04-00026" ref-type="bibr">45</xref>].</p></sec><sec id="sec2dot3-diseases-04-00026"><title>2.3. Coronavirus Assembly and Egress</title><p>The assembly of virions is quickly ensued with the accumulation of new genomic RNA and structural components. In this phase of the infection cycle, the helical nucleocapsid containing the genomic RNA interacts with other viral structural proteins (S, E and M proteins) to form the assembled virion. The assembly of CoV particles is completed through budding of the helical nucleocapsid through membranes early in the secretory pathway from the endoplasmic reticulum to the Golgi intermediate compartment (ERGIC). The contributions of the host in this phase of the infection cycle have rarely been explored. Currently, it is known that the M protein orchestrates the entire assembly process by selecting and organizing the viral envelope components at the assembly sites and by mediating the interactions with the nucleocapsid to allow the budding of virions [<xref rid="B46-diseases-04-00026" ref-type="bibr">46</xref>]. The M protein interacts with different viral structural proteins, such as the E protein, to assemble into a mature virus. This interaction generates the scaffold of the virion envelope and induces the budding and release of the M protein-modified membrane and with the S protein to assemble the spikes into the viral envelope [<xref rid="B46-diseases-04-00026" ref-type="bibr">46</xref>,<xref rid="B47-diseases-04-00026" ref-type="bibr">47</xref>]. Following assembly and budding, the virions are transported in vesicles and eventually released by exocytosis. In a recent study, an inhibition of a Valosin-containing protein (VCP/p97) resulted in virus accumulation in early endosome in infectious bronchitis virus (IBV), suggesting a role for VCP in the maturation of virus-loaded endosomes [<xref rid="B48-diseases-04-00026" ref-type="bibr">48</xref>].</p></sec></sec><sec id="sec3-diseases-04-00026"><title>3. Human Coronavirus Infection and Apoptosis</title><p>Apoptosis is a process of programmed cell death that is tightly regulated and anti-inflammatory. When cells undergo apoptosis, they demonstrate specific hallmarks such as cell shrinkage, extensive plasma membrane blebbing, nuclear pykosis, DNA fragmentation and asymmetrical distribution of plasma membrane [<xref rid="B49-diseases-04-00026" ref-type="bibr">49</xref>,<xref rid="B50-diseases-04-00026" ref-type="bibr">50</xref>,<xref rid="B51-diseases-04-00026" ref-type="bibr">51</xref>]. To date, two main mechanisms of apoptosis have been established—the extrinsic and intrinsic pathways. The extrinsic pathway is initiated by the binding of extracellular death ligands (such as Fas ligand (FasL) and TNF-receptor-related apoptosis-inducing ligands (TRAIL)) to death receptors from the tumour necrosis factor (TNF) super-family [<xref rid="B52-diseases-04-00026" ref-type="bibr">52</xref>]. These death receptors then recruit various death adapter proteins, such as Fas-associated death domain protein (FADD) [<xref rid="B53-diseases-04-00026" ref-type="bibr">53</xref>], and initiator procaspases 8 and 10 to form the death-inducing signalling complex (DISC) [<xref rid="B54-diseases-04-00026" ref-type="bibr">54</xref>,<xref rid="B55-diseases-04-00026" ref-type="bibr">55</xref>]. Consequently, the two initiator procapases are cleaved to their active forms and induce a signalling cascade to eventually activate effector caspases 3 and 7. On the other hand, the intrinsic pathway occurs internally in the cell and involves changes in the mitochondrial outer membrane permeability (MOMP) based on the ratio of pro-apoptotic and anti-apoptotic B-cell lymphoma 2 (Bcl2) family of proteins (<xref ref-type="fig" rid="diseases-04-00026-f003">Figure 3</xref>). Enhanced MOMP causes the release of pro-apoptotic factors such as cytochrome c to activate initiator caspase 9. Like the extrinsic pathway, activation of initiator caspase 9 in the intrinsic pathway results in the proteolytic cleavage effector caspases 3 and 7, which in turn process many key cellular proteins essential for apoptosis [<xref rid="B56-diseases-04-00026" ref-type="bibr">56</xref>]. Convergence between the two pathways may also occur even before effector caspase activation, when Bid, a pro-apoptotic Bcl2 family protein, is directly cleaved by caspase 8 [<xref rid="B57-diseases-04-00026" ref-type="bibr">57</xref>].</p><p>During viral infections, apoptosis is induced as one of the host antiviral responses to limit virus replication and production. Many viruses have evolved distinct strategies to subvert apoptosis [<xref rid="B58-diseases-04-00026" ref-type="bibr">58</xref>]. For example, some viruses encode for viral proteins that act as Bcl2 family protein homologues [<xref rid="B59-diseases-04-00026" ref-type="bibr">59</xref>]. Alternatively, viruses might develop mechanisms to regulate Bcl2 family proteins or caspase activation either directly or indirectly through other molecular pathways such as mitogen-activated protein (MAPK) and nuclear factor kappa B (NF-κB) pathways [<xref rid="B60-diseases-04-00026" ref-type="bibr">60</xref>,<xref rid="B61-diseases-04-00026" ref-type="bibr">61</xref>,<xref rid="B62-diseases-04-00026" ref-type="bibr">62</xref>,<xref rid="B63-diseases-04-00026" ref-type="bibr">63</xref>,<xref rid="B64-diseases-04-00026" ref-type="bibr">64</xref>,<xref rid="B65-diseases-04-00026" ref-type="bibr">65</xref>]. Interestingly, some viruses may engage the apoptotic machineries for efficient viral infection. For instance, alphaviruses and flaviviruses contain phosphatidylserine-rich viral membranes to imitate apoptotic cells to promote viral entry [<xref rid="B66-diseases-04-00026" ref-type="bibr">66</xref>].</p><sec id="sec3dot1-diseases-04-00026"><title>3.1. Cell Tropism and Apoptosis</title><p>As HCoVs are respiratory pathogens known to infect tissue cultures and cell lines derived from the respiratory tract, these viruses may also infect other tissue cultures and cell lines. Infection of these tissues and cells may induce apoptosis [<xref rid="B67-diseases-04-00026" ref-type="bibr">67</xref>,<xref rid="B68-diseases-04-00026" ref-type="bibr">68</xref>]. However, although HCoVs mainly target the respiratory tract during infection, they have also been associated to apoptosis induction in a wide spectrum of cell types, including intestinal mucosal cells, kidney tubular cells and neuronal cells [<xref rid="B69-diseases-04-00026" ref-type="bibr">69</xref>,<xref rid="B70-diseases-04-00026" ref-type="bibr">70</xref>,<xref rid="B71-diseases-04-00026" ref-type="bibr">71</xref>,<xref rid="B72-diseases-04-00026" ref-type="bibr">72</xref>,<xref rid="B73-diseases-04-00026" ref-type="bibr">73</xref>,<xref rid="B74-diseases-04-00026" ref-type="bibr">74</xref>]. Autopsy studies of SARS-CoV-infected tissues revealed apoptosis induced in lung, spleen and thyroid [<xref rid="B75-diseases-04-00026" ref-type="bibr">75</xref>]. HCoVs have also been shown to infect the immune system and induce apoptosis in immune cells such as macrophages, monocytes, T lymphocytes and dendritic cells [<xref rid="B69-diseases-04-00026" ref-type="bibr">69</xref>,<xref rid="B76-diseases-04-00026" ref-type="bibr">76</xref>,<xref rid="B77-diseases-04-00026" ref-type="bibr">77</xref>,<xref rid="B78-diseases-04-00026" ref-type="bibr">78</xref>,<xref rid="B79-diseases-04-00026" ref-type="bibr">79</xref>]. Because these immune cells are associated with the activation of the innate and acquired immunity, it is reasonable to speculate that the massive elimination of these cells could be a viral strategy to suppress the host innate and adaptive immune responses. In a recent study, it was reported that HCoV-229E infection resulted in massive CPE and cell death in dendritic cells [<xref rid="B80-diseases-04-00026" ref-type="bibr">80</xref>]. Since dendritic cells are prevalent throughout our bodies, it is possible that they are used as a vehicle to facilitate viral spread and impair our immune systems [<xref rid="B80-diseases-04-00026" ref-type="bibr">80</xref>,<xref rid="B81-diseases-04-00026" ref-type="bibr">81</xref>].</p></sec><sec id="sec3dot2-diseases-04-00026"><title>3.2. Molecular Mechanisms in Apoptosis</title><p>On a molecular level, HCoV infections have been reported to trigger apoptosis through multiple mechanisms. SARS-CoV-induced apoptosis was shown to be caspase-dependent and could be inhibited by caspase inhibitor Z-VAD-FMK or overexpression of Bcl2 [<xref rid="B82-diseases-04-00026" ref-type="bibr">82</xref>,<xref rid="B83-diseases-04-00026" ref-type="bibr">83</xref>]. Although viral replication was required for apoptosis induction [<xref rid="B83-diseases-04-00026" ref-type="bibr">83</xref>], apoptosis did not affect the viral replication kinetics of SARS-CoV [<xref rid="B82-diseases-04-00026" ref-type="bibr">82</xref>]. On the other hand, infection of primary T lymphocytes by MERS-CoV was shown to induce DNA fragmentation and caspase 8 and 9 activation, suggesting that both extrinsic and intrinsic pathways were activated. Unlike SARS-CoV infection, MERS-CoV replication was not necessary to induce apoptosis in infected T lymphocytes [<xref rid="B79-diseases-04-00026" ref-type="bibr">79</xref>]. Apoptosis can also be induced by the less pathogenic strains of HCoVs, as substantiated by microarray data showing significant changes in pro-apoptotic and anti-apoptotic gene expression of Bcl2 family members during HCoV-229E infection [<xref rid="B84-diseases-04-00026" ref-type="bibr">84</xref>]. Infection of HCoV-OC43 was shown to promote BAX translocation to the mitochondria in human neuronal cells [<xref rid="B74-diseases-04-00026" ref-type="bibr">74</xref>]. Although caspases 3 and 9 were activated in HCoV-OC43-infected murine and human neuronal cells [<xref rid="B9-diseases-04-00026" ref-type="bibr">9</xref>,<xref rid="B74-diseases-04-00026" ref-type="bibr">74</xref>], addition of pan-caspase inhibitor Z-VAD-FMK and the caspase-9 inhibitor Z-LEHD-FMK did not affect the viability of these infected neuronal cells, indicating that programmed cell death induced by HCoV-OC43 could be caspase-independent [<xref rid="B74-diseases-04-00026" ref-type="bibr">74</xref>]. This highlights the possibility of a non-classical programmed cell death mechanism induced in HCoV infection.</p><p>Apoptotic mechanisms during HCoV infection are likely to be manipulated by viral proteins (<xref ref-type="fig" rid="diseases-04-00026-f004">Figure 4</xref>), although this has only mostly been studied in SARS-CoV. Specifically, SARS-CoV S, N, E, M, ORF-6, 7a and 9b proteins have been shown to serve pro-apoptotic functions in their host cells [<xref rid="B77-diseases-04-00026" ref-type="bibr">77</xref>,<xref rid="B85-diseases-04-00026" ref-type="bibr">85</xref>,<xref rid="B86-diseases-04-00026" ref-type="bibr">86</xref>,<xref rid="B87-diseases-04-00026" ref-type="bibr">87</xref>,<xref rid="B88-diseases-04-00026" ref-type="bibr">88</xref>,<xref rid="B89-diseases-04-00026" ref-type="bibr">89</xref>,<xref rid="B90-diseases-04-00026" ref-type="bibr">90</xref>,<xref rid="B91-diseases-04-00026" ref-type="bibr">91</xref>]. Expression of SARS-CoV E protein and 7a protein promoted mitochondrial-mediated apoptosis by sequestering the anti-apoptotic Bcl-XL protein to the endoplasmic reticulum (ER) membranes [<xref rid="B77-diseases-04-00026" ref-type="bibr">77</xref>,<xref rid="B92-diseases-04-00026" ref-type="bibr">92</xref>]. SARS-CoV M protein is also highly pro-apoptotic and mediates activation of both caspases 8 and 9 [<xref rid="B90-diseases-04-00026" ref-type="bibr">90</xref>]. Additionally, HCoV-OC43 wild type S protein has been shown to induce unfolded protein response (UPR) in human neuronal NT2-N and LA-N-5 cell lines, which may lead to apoptosis [<xref rid="B93-diseases-04-00026" ref-type="bibr">93</xref>]. A recombinant HCoV-OC43 harbouring point mutations at its S protein induced stronger caspase 3 activation and nuclear fragmentation than the wild-type virus [<xref rid="B93-diseases-04-00026" ref-type="bibr">93</xref>]. It is interesting to note that the localisation of SARS-CoV N and 9b protein is associated with induction of caspase-dependent apoptosis [<xref rid="B89-diseases-04-00026" ref-type="bibr">89</xref>,<xref rid="B94-diseases-04-00026" ref-type="bibr">94</xref>]. This finding opens up to novel perspectives of the link between subcellular localisation of viral proteins and caspase activation as a mode of apoptosis regulation by HCoVs.</p></sec></sec><sec id="sec4-diseases-04-00026"><title>4. Human Coronavirus Infection and Innate Immunity</title><p>When the cells are exposed to pathogens such as viruses, immune responses are induced as a form of host defence. The immune response is modulated during pathogen exposure in a cell-type dependent fashion. Innate immunity is the first line of defence mounted against the virus before the adaptive immune system is generated. Both the host and virus can manipulate innate immune mechanisms as a form of defence or evasion strategy [<xref rid="B95-diseases-04-00026" ref-type="bibr">95</xref>,<xref rid="B96-diseases-04-00026" ref-type="bibr">96</xref>].</p><sec id="sec4dot1-diseases-04-00026"><title>4.1. Pattern Recognition Receptors</title><p>Cells in the immune system detect the viral pathogens via several recognition strategies. Of which, the most well characterized is the pattern recognition receptors (PRR), which engage various microbial pathogens via evolutionarily conserved structures known as pathogen-associated molecular patterns (PAMPs). PRRs are mainly categorized into three classes, namely Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and nucleotide oligomerisation domain (NOD)-like receptors (NLRs).</p><p>TLR is a type I transmembrane protein localized to either the cell surface or endosomal vesicles. Their leucine-rich repeats (LRR) domain mediates the recognition of PAMPs and damage-associated molecular patterns (DAMPs) from various sources including bacteria, fungi and viruses [<xref rid="B97-diseases-04-00026" ref-type="bibr">97</xref>]. Activation of TLRs occurs mainly in antigen-presenting cells such as dendritic cells (DCs), macrophages, monocytes and B cells. Of the 10 known TLRs in human, TLR2, 3, 4, 7 and 9 are found to be involved in viral detection [<xref rid="B98-diseases-04-00026" ref-type="bibr">98</xref>,<xref rid="B99-diseases-04-00026" ref-type="bibr">99</xref>]. TLR3 recognizes double-stranded RNA (dsRNA), a replicative intermediate produced during viral RNA replication [<xref rid="B100-diseases-04-00026" ref-type="bibr">100</xref>]. TLR7 and 8 detect single-stranded RNA (ssRNA) and TLR9 recognizes unmethylated CpG DNA present in DNA viruses [<xref rid="B101-diseases-04-00026" ref-type="bibr">101</xref>,<xref rid="B102-diseases-04-00026" ref-type="bibr">102</xref>,<xref rid="B103-diseases-04-00026" ref-type="bibr">103</xref>]. Besides nucleic acids, other TLRs, such as TLR2 and 4, sense viral proteins as exemplified in respiratory syncytial virus (RSV), hepatitis virus, measles virus and human immunodeficiency virus [<xref rid="B104-diseases-04-00026" ref-type="bibr">104</xref>,<xref rid="B105-diseases-04-00026" ref-type="bibr">105</xref>,<xref rid="B106-diseases-04-00026" ref-type="bibr">106</xref>,<xref rid="B107-diseases-04-00026" ref-type="bibr">107</xref>]. Upon recognition of viral components, TLRs recruit Toll/interleukin-1 receptor (TIR)-containing signalling adaptor molecules, such as MyD88 (myeloid differentiation primary response protein 88) and TIR-domain-containing adapter-inducing interferon-β (TRIF) [<xref rid="B108-diseases-04-00026" ref-type="bibr">108</xref>,<xref rid="B109-diseases-04-00026" ref-type="bibr">109</xref>,<xref rid="B110-diseases-04-00026" ref-type="bibr">110</xref>]. MyD88 and TRIF then stimulate the MAPK and NF-κB pathways to boost IFN and pro-inflammatory cytokine production [<xref rid="B111-diseases-04-00026" ref-type="bibr">111</xref>].</p><p>Unlike TLRs, RLRs and NLRs are expressed ubiquitously. RLRs are a family of cytoplasmic receptors that comprise of three members: retinoic acid-inducible gene I (RIG-I), melanoma differentiation associated factor 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2). RIG-I and MDA5 possess two caspase-recruitment domains (CARDs) at their N terminal, a DExD/H-box RNA helicase domain (where x can be any amino acid) and a repressor domain (RD) at the C terminal. On the other hand, LGP2 lacks the CARD domain [<xref rid="B112-diseases-04-00026" ref-type="bibr">112</xref>], and it regulates RIG-I and MDA5 either positively or negatively [<xref rid="B113-diseases-04-00026" ref-type="bibr">113</xref>,<xref rid="B114-diseases-04-00026" ref-type="bibr">114</xref>,<xref rid="B115-diseases-04-00026" ref-type="bibr">115</xref>]. RIG-I recognizes 5′-triphosphate moieties present in viral genomic RNA, as well as double-stranded “panhandle” structure formed by self-annealing of complementary ends of the viral genome [<xref rid="B116-diseases-04-00026" ref-type="bibr">116</xref>,<xref rid="B117-diseases-04-00026" ref-type="bibr">117</xref>]. In contrast, MDA5 usually detects dsRNA sequences of longer length. Binding of RIG-I and MDA5 to the viral RNA causes a conformational change to expose the CARD domain. An adaptor protein known as mitochondrial antiviral signalling adaptor, MAVS, which is localized at the mitochondria and peroxisomes, is recruited. MAVS then activates transcription factors such as interferon regulatory factor 1 (IRF1), IRF3 and NF-κB to trigger the expression of interferons (IFNs) and pro-inflammatory cytokines [<xref rid="B117-diseases-04-00026" ref-type="bibr">117</xref>] (<xref ref-type="fig" rid="diseases-04-00026-f005">Figure 5</xref>).</p><p>NLRs are another large family of cytosolic proteins that are organized into three main domains: a CARD domain, pyrin domain (PYD), or baculovirus inhibitor repeat domain at the N terminal, a conserved NOD motif at the intermediate region and LRR motifs at the C terminal. The LRR motifs detect viral PAMPs to induce a structural rearrangement. Subsequently, a diverse range of signalling pathways, including MAPK and NF-κB pathways, is activated [<xref rid="B118-diseases-04-00026" ref-type="bibr">118</xref>], Furthermore, assembly of multimeric protein complexes known as inflammasomes is mediated by some NLR family members such as NLR family PYD-containing 1 (NLRP1), NLRP3 and NLR family CARD-containing 4 (NLRC4). These inflammasomes activate inflammatory caspase, capase-1, that induces the cleavage of pro-IL-1β and pro-IL-18 into their active forms [<xref rid="B119-diseases-04-00026" ref-type="bibr">119</xref>].</p></sec><sec id="sec4dot2-diseases-04-00026"><title>4.2. Interferon Responses</title><p>IFNs are classified into type I, II and III based on their preference for specific IFN receptors. In particular, type I IFN is best known for its antiviral actions. Binding of type I IFNs to the IFN-α/β receptor (IFNAR) induces the oligomerisation of its receptor subunits, IFN-αR1 and IFN-αR2, and consequently conveys downstream signalling via the Janus kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway. Autophosphorylation of JAK domains in the IFNAR results in subsequent phosphorylation of STAT1 and STAT2 proteins at their tyrosine residues. This is followed by dimerisation and nuclear translocation of the activated STAT proteins, which recruit IFN regulatory factor 9 (IRF9) to form the IFN-stimulated gene factor 3 (ISGF3). ISFG3 is a transcription factor that binds to its cognate DNA sequence known as IFN-stimulated response elements (ISREs) to activate transcription of IFN-stimulated genes (ISGs) [<xref rid="B120-diseases-04-00026" ref-type="bibr">120</xref>] (<xref ref-type="fig" rid="diseases-04-00026-f005">Figure 5</xref>). Many of these ISGs such as 2′–5′ oligoadenylatesynthetase and protein kinase R (PKR) confer resistance against virus invasions [<xref rid="B121-diseases-04-00026" ref-type="bibr">121</xref>]. Additionally, type I IFNs facilitates the maturation of dendritic cells (DCs), cytotoxicity of natural killer (NK) cells, and differentiation of T lymphocytes [<xref rid="B98-diseases-04-00026" ref-type="bibr">98</xref>].</p></sec><sec id="sec4dot3-diseases-04-00026"><title>4.3. Modulation of Innate Immunity</title><p>Infection by HCoVs, especially the highly pathogenic SARS-CoV and MERS-CoV, is associated with suppression of IFN synthesis [<xref rid="B122-diseases-04-00026" ref-type="bibr">122</xref>,<xref rid="B123-diseases-04-00026" ref-type="bibr">123</xref>,<xref rid="B124-diseases-04-00026" ref-type="bibr">124</xref>,<xref rid="B125-diseases-04-00026" ref-type="bibr">125</xref>,<xref rid="B126-diseases-04-00026" ref-type="bibr">126</xref>]. The capability of the virus to regulate type I IFN signalling is an important hallmark for virulence [<xref rid="B127-diseases-04-00026" ref-type="bibr">127</xref>]. As compared to SARS-CoV and MERS-CoV, a huge rise in type I IFNs were detected in cells infected with HCoV strain 229E [<xref rid="B80-diseases-04-00026" ref-type="bibr">80</xref>,<xref rid="B124-diseases-04-00026" ref-type="bibr">124</xref>,<xref rid="B128-diseases-04-00026" ref-type="bibr">128</xref>].</p><p>Based on studies from SARS-CoV and Mouse Hepatitis Virus (MHV)-infected cells, two mechanisms have been proposed to explain the HCoV-mediated inhibition of type I IFN production [<xref rid="B13-diseases-04-00026" ref-type="bibr">13</xref>,<xref rid="B126-diseases-04-00026" ref-type="bibr">126</xref>]. Firstly, CoV genomic and subgenomic RNA replication takes place in double membrane vesicles to prevent detection by PRRs [<xref rid="B13-diseases-04-00026" ref-type="bibr">13</xref>,<xref rid="B129-diseases-04-00026" ref-type="bibr">129</xref>]. Secondly, proteins encoded by the virus could interfere with innate immune pathways [<xref rid="B13-diseases-04-00026" ref-type="bibr">13</xref>,<xref rid="B130-diseases-04-00026" ref-type="bibr">130</xref>]. The structural proteins, nonstructural proteins and accessory proteins of HCoVs have been shown to modify innate immune responses (<xref ref-type="fig" rid="diseases-04-00026-f005">Figure 5</xref>).</p><sec id="sec4dot3dot1-diseases-04-00026"><title>4.3.1. Viral Proteins Involved in Innate Immunity</title><sec><title>Structural Proteins of HCoVs</title><p>Expression of SARS-CoV M protein could suppress type I IFN production mediated by RIG-I, but not MDA5, in infected HEK293 cells [<xref rid="B131-diseases-04-00026" ref-type="bibr">131</xref>], likely through its first transmembrane domain. However, this inhibition was not observed when expressing the M protein of HCoV-HKU1, suggesting that this activity is not conserved among all HCoV strains [<xref rid="B132-diseases-04-00026" ref-type="bibr">132</xref>]. In another study, it was shown that the MERS-CoV M protein could also suppress type I IFN by inhibiting the translocation of IRF3 into the nucleus, although the exact mechanism has not yet been elucidated [<xref rid="B133-diseases-04-00026" ref-type="bibr">133</xref>]. Additionally, SARS-CoV N protein was also shown to interfere with the function of IRF3 [<xref rid="B134-diseases-04-00026" ref-type="bibr">134</xref>]. The N protein of SARS-CoV likely act at the initial recognition stage of viral RNA via its RNA binding activity, although it neither forms a complex with RIG-I nor MDA5 [<xref rid="B135-diseases-04-00026" ref-type="bibr">135</xref>]. This implies that the N protein possibly acts on other viral RNA recognition strategies of the host.</p></sec><sec><title>Non-Structural and Accessory Proteins of HCoVs</title><p>Besides the structural proteins, other nonstructural proteins (nsp) and accessory proteins of HCoVs have also been implicated in the modulation of innate immunity. For instance, nsp1 of both SARS-CoV and MERS-CoV has been demonstrated to modify capped non-viral RNAs to facilitate endonucleolytic cleavage of host messenger RNA (mRNA) [<xref rid="B136-diseases-04-00026" ref-type="bibr">136</xref>,<xref rid="B137-diseases-04-00026" ref-type="bibr">137</xref>]. Additionally, SARS-CoV nsp1 interacted with the 40S subunit of ribosome to prevent host mRNA translation [<xref rid="B136-diseases-04-00026" ref-type="bibr">136</xref>]. This induces the host shutoff mechanism, as transcription and translation of viral RNA are more favoured over that of host mRNA. In a recent study, several residues of SARS-CoV nsp1 were identified to affect IFN-dependent signalling [<xref rid="B138-diseases-04-00026" ref-type="bibr">138</xref>]. In addition to nsp1, SARS-CoV and MERS-CoV nsp3 proteins, which possess papain-like protease (PLpro) domain and a PLP2 domain, also antagonize IFN production. Both SARS-CoV and MERS-CoV PLpro domains are deISGylating enzymes and they downregulated mRNA levels of pro-inflammatory cytokines including CCL5, IFNβ, and CXCL10 [<xref rid="B139-diseases-04-00026" ref-type="bibr">139</xref>]. Suppression of IFN responses by SARS-CoV PLpro is not mediated by its protease activity. Rather, SARS-CoV PLpro inhibited the phosphorylation of interferon-regulatory factor 3 (IRF3) and its translocation to the nucleus to enhance IFN gene transcription [<xref rid="B140-diseases-04-00026" ref-type="bibr">140</xref>]. Expression of MERS-CoV PLpro also antagonizes IFN production and is required for suppression on RIG-I and MDA5 [<xref rid="B139-diseases-04-00026" ref-type="bibr">139</xref>,<xref rid="B141-diseases-04-00026" ref-type="bibr">141</xref>]. Furthermore, it has been identified that the ADP-ribose-1-monophosphatase macrodomain encoded within nsp3 in HCoV-229E and SARS-CoV is responsible for suppressing IFN induction [<xref rid="B142-diseases-04-00026" ref-type="bibr">142</xref>].</p><p>Despite being dispensable in viral replication, HCoV accessory proteins are essential in diverse cellular signalling, such as cell proliferation, apoptosis and interferon signalling [<xref rid="B25-diseases-04-00026" ref-type="bibr">25</xref>]. In SARS-CoV, ORF3b and -6 are shown to interfere with IFNβ synthesis by inhibiting the phosphorylation and nuclear translocation of IRF3. Furthermore, these accessory proteins also disrupt IFN signalling by preventing IFNβ-induced activation of interferon-stimulated response element (ISRE) found in the promoter region of ISG [<xref rid="B134-diseases-04-00026" ref-type="bibr">134</xref>]. The accessory proteins of MERS-CoV, ORF4a, -4b and -5, could similarly suppress IRF3 nuclear translocation, hence significantly reducing IFN-β promoter-driven luciferase activity in cells transfected with these accessory proteins [<xref rid="B133-diseases-04-00026" ref-type="bibr">133</xref>].</p></sec></sec></sec></sec><sec id="sec5-diseases-04-00026"><title>5. Human Coronavirus and ER Stress Response</title><p>The endoplasmic reticulum (ER) is a cellular organelle important for protein synthesis, folding, processing and post-translational modifications. In normal circumstances, the ER can be loaded with a very high concentration of proteins without perturbing its unique luminal environment [<xref rid="B143-diseases-04-00026" ref-type="bibr">143</xref>]. However, when the protein load exceeds the ER folding and processing capacity, rapid accumulation of misfolded or unfolded proteins occurs within the ER lumen. Various signalling pathways, collectively known as ER stress response or UPR, are activated. These pathways are initiated by three ER transmembrane sensors-protein-kinase-R (PKR)-like endoplasmic reticulum kinase (PERK), inositol-requiring protein 1 (IRE1) and activating transcriptional factor 6 (ATF6) to orchestrate the restoration of ER homeostasis by enhancing protein folding, attenuating protein translation and upregulating genes related to protein folding, chaperoning and ER-assisted degradation (ERAD) (<xref ref-type="fig" rid="diseases-04-00026-f006">Figure 6</xref>). In cases of prolonged and irreversible ER stress, apoptosis mechanisms are triggered [<xref rid="B144-diseases-04-00026" ref-type="bibr">144</xref>]. During viral infections, ER stress response is induced. This massive utilisation of the ER elicit immense burden, causing the host to mount UPR as its antiviral response [<xref rid="B145-diseases-04-00026" ref-type="bibr">145</xref>].</p><sec id="sec5dot1-diseases-04-00026"><title>5.1. PERK Signalling Pathway</title><p>Activation of PERK is initiated by its dissociation of the luminal domain from the ER chaperone, binding immunoglobulin protein (BiP). This is followed by the oligomerisation and autophosphorylation of PERK. In its active form, PERK phosphorylates Ser51 at the α-subunit of eukaryotic initiation factor 2 (eIF2α) to attenuate protein translation [<xref rid="B146-diseases-04-00026" ref-type="bibr">146</xref>]. Activation of PERK plays a pro-survival role in cells, as clearly demonstrated by PERK−/− mouse embryonic fibroblasts, which exhibited higher cell death when treated with cycloheximide, an ER stress-inducing agent [<xref rid="B147-diseases-04-00026" ref-type="bibr">147</xref>]. Phosphorylated eIF2α not only triggers a shutdown of global protein synthesis, but also enhances the translation of activating transcription factor ATF4 [<xref rid="B148-diseases-04-00026" ref-type="bibr">148</xref>]. ATF4 stimulates target gene expression such as GADD153 (also known as CHOP or C/EBP-homologous protein), to enhance transcription of pro-apoptotic genes [<xref rid="B149-diseases-04-00026" ref-type="bibr">149</xref>]. Additionally, eIF2α can be phosphorylated by other kinases such as PKR, heme-regulated inhibitor kinase (HRI), and general control non-derepressible-2 (GCN2) [<xref rid="B144-diseases-04-00026" ref-type="bibr">144</xref>]. These kinases activate various downstream signalling pathways, which together form the integrated stress response [<xref rid="B146-diseases-04-00026" ref-type="bibr">146</xref>,<xref rid="B150-diseases-04-00026" ref-type="bibr">150</xref>].</p><p>PKR and eIF2α phosphorylation was detected in SARS-CoV-infected cells and inhibition of PKR using antisense peptide-conjugated phosphorodiamidate morpholino oligomers did not affect eIF2α phosphorylation but significantly reduced SARS-CoV-induced apoptosis. SARS-CoV protein replication and virus production were not affected by PKR knockdown. Therefore, it is likely that SARS-CoV adopts a strategy to counteract against the antiviral effects of PKR, thus enabling viral mRNA translation to proceed regardless of eIF2α phosphorylation. PERK was also found to be activated during SARS-CoV infection [<xref rid="B75-diseases-04-00026" ref-type="bibr">75</xref>], possibly through its S and 3a proteins [<xref rid="B151-diseases-04-00026" ref-type="bibr">151</xref>,<xref rid="B152-diseases-04-00026" ref-type="bibr">152</xref>]. In another study, it was demonstrated that expression of a dominant-negative PERK mutant, that inhibited PERK kinase activity, suppressed the transcriptional activation of Grp78 and Grp94 promoters mediated by S proteins of SARS-CoV and HCoV-HKU1 [<xref rid="B153-diseases-04-00026" ref-type="bibr">153</xref>]. However, PERK activation is unlikely to occur in all HCoV strains. In neuronal cells lines infected with HCoV-OC43, it was shown that eIF2α was only transiently phosphorylated at the early stage of infection, but was subsequently suppressed and returned back to its basal level of phosphorylation, similar to the mock-infected cells [<xref rid="B93-diseases-04-00026" ref-type="bibr">93</xref>]. On the other hand, previous studies from this group showed that PKR, PERK and eIF2α were moderately induced at the early stages of IBV infection, but were subsequently suppressed at late infection stages [<xref rid="B154-diseases-04-00026" ref-type="bibr">154</xref>,<xref rid="B155-diseases-04-00026" ref-type="bibr">155</xref>]. Nevertheless, the moderate and transient increase in eIF2α phosphorylation was sufficient to activate ATF4 protein translation and upregulate the downstream targets of ATF4, ATF3 and GADD153. Knockdown of PKR and PERK in IBV-infected cells attenuated IBV-induced GADD153 upregulation and IBV-induced apoptosis, although the viral protein replication was unaffected [<xref rid="B155-diseases-04-00026" ref-type="bibr">155</xref>]. Upregulation of GADD153 is postulated to induce pro-apoptotic protein TRIB3 and inhibit pro-survival ERK protein [<xref rid="B154-diseases-04-00026" ref-type="bibr">154</xref>], as well as provide a negative feedback to rapidly dephosphorylate eIF2α at late stages of IBV infection [<xref rid="B155-diseases-04-00026" ref-type="bibr">155</xref>]. Based on these findings, we speculate the HCoVs might use similar mechanism to modulate the PKR/PERK/eIF2α pathway in infected cells. More studies could be done on HCoV infection to analyze the activation of the PKR/PERK/eIF2α pathway at various stages of infection.</p></sec><sec id="sec5dot2-diseases-04-00026"><title>5.2. ATF6 Signalling Pathway</title><p>Like PERK, activation of ATF6 is initiated by dissociation from the ER chaperone, BiP, although alternative mechanisms such as deglycosylation and reduction of disulphide bonds could occur [<xref rid="B156-diseases-04-00026" ref-type="bibr">156</xref>,<xref rid="B157-diseases-04-00026" ref-type="bibr">157</xref>]. ATF6 then translocates into the Golgi apparatus, where it is proteolyzed by site-1 and site-2 proteases (S1P and S2P). The processed ATF6 then migrates to the nucleus where it turns on expression of genes containing an ER stress response element (ERSE) in their promoters [<xref rid="B158-diseases-04-00026" ref-type="bibr">158</xref>]. Like ATF4, ATF6 also induces expression of ER chaperone proteins such as GRP78, GRP94 and transcription factors CHOP and X box-binding protein 1 (XBP1) [<xref rid="B150-diseases-04-00026" ref-type="bibr">150</xref>]. XBP1 is essential for IRE signalling [<xref rid="B159-diseases-04-00026" ref-type="bibr">159</xref>].</p><p>As compared to the two other UPR branches, PERK and IRE1, the ATF6 branch is less well studied. As GRP94/78 are also target genes of ATF6, and their promoter activities were enhanced by SARS-CoV S protein, one could hypothesize that ATF6 pathway could also be induced by SARS-CoV S. Surprisingly, overexpression of SARS-CoV S protein did not affect ATF6 promoter luciferase activity [<xref rid="B152-diseases-04-00026" ref-type="bibr">152</xref>]. Deletion of E protein in recombinant SARS-CoV also did not significantly activate ATF6 [<xref rid="B91-diseases-04-00026" ref-type="bibr">91</xref>]. Intriguingly, 8ab protein, an accessory protein of SARS-CoV, was shown to reside in the luminal surface of the ER surface and activate ATF6 via facilitating its proteolysis and translocation of the processed ATF6 into the nucleus [<xref rid="B160-diseases-04-00026" ref-type="bibr">160</xref>]. 8ab protein from SARS-CoV was found in civet cats and early human isolates, but was subsequently split into two accessory proteins, 8a and 8b, with a characteristic 29-nucleotide deletion [<xref rid="B161-diseases-04-00026" ref-type="bibr">161</xref>].</p></sec><sec id="sec5dot3-diseases-04-00026"><title>5.3. IRE1 Signalling Pathway</title><p>IRE1 is believed to be the last UPR branch to be activated in cells undergoing ER stress [<xref rid="B162-diseases-04-00026" ref-type="bibr">162</xref>]. It is also the most conserved among all UPR arms [<xref rid="B163-diseases-04-00026" ref-type="bibr">163</xref>]. Although IRE1 was initially proposed to be activated in the same mechanism as PERK [<xref rid="B162-diseases-04-00026" ref-type="bibr">162</xref>], later studies suggested that the N-terminal luminal domain (NLD) of IRE1 can directly bind unfolded proteins [<xref rid="B164-diseases-04-00026" ref-type="bibr">164</xref>,<xref rid="B165-diseases-04-00026" ref-type="bibr">165</xref>]. Activation of its RNase domain results in unconventional splicing of a 252-nucleotide intron from homologous to Atf/Creb1 (HAC1) mRNA in yeasts and a 26-nucleotide intron from X-box binding protein 1 (XBP1) mRNA in humans [<xref rid="B166-diseases-04-00026" ref-type="bibr">166</xref>]. Splicing of XBP1 generates a potent transcription factor, XBP1s, that induces expression of genes related to protein entry into the ER, folding and ERAD [<xref rid="B159-diseases-04-00026" ref-type="bibr">159</xref>]. In a negative feedback mechanism, XBP1s also promotes the transcription of E3 ubiquitin ligase synoviolin to enhance IRE1 ubiquitination [<xref rid="B167-diseases-04-00026" ref-type="bibr">167</xref>]. The unspliced variant XBP1u contained a nuclear exclusion signal to sequester XBP1s from the nucleus, thus making XBP1u another negative feedback regulator of XBP1s. [<xref rid="B168-diseases-04-00026" ref-type="bibr">168</xref>]. In a separate mechanism, IRE1 can cleave ER-associated mRNA species through regulated IRE1-dependent decay (RIDD) during late stages of ER stress [<xref rid="B145-diseases-04-00026" ref-type="bibr">145</xref>]. It is believed that initial XBP1/HAC1 splicing by IRE1 promotes survival but subsequent activation of RIDD upon prolonged ER stress leads to cell death, thus allowing IRE1 to play dual role in apoptosis [<xref rid="B169-diseases-04-00026" ref-type="bibr">169</xref>,<xref rid="B170-diseases-04-00026" ref-type="bibr">170</xref>]. Another important enzymatic activation of IRE1 is its kinase activity. The kinase domain of phosphorylated IRE1 recruits the TNF receptor-associated factor 2 (TRAF2), which then activates other kinases to eventually activate the c-Jun N-terminal kinase (JNK) and regulates ER stress-dependent apoptosis [<xref rid="B171-diseases-04-00026" ref-type="bibr">171</xref>].</p><p>Previous studies have investigated the role of IRE1-XBP1 pathway during SARS-CoV infection. Although no increase in XBP1 splicing was observed in SARS-CoV-infected cells [<xref rid="B172-diseases-04-00026" ref-type="bibr">172</xref>], deletion of E protein in recombinant SARS-CoV resulted in significant XBP1 splicing and higher rate of apoptosis [<xref rid="B91-diseases-04-00026" ref-type="bibr">91</xref>]. On the other hand, infection of HCoV-OC43 caused an induction in XBP1 splicing and enhanced expression of genes regulated by XBP1s, namely Edem, Herp, Grp94 and P58-ipk. However, introduction of two point mutations (H183R and Y241H) in the S protein of HCoV-OC43 led to a higher degree of XBP1 cleavage, followed by a strong activation of caspase-3 and nuclear fragmentation [<xref rid="B93-diseases-04-00026" ref-type="bibr">93</xref>]. Since IRE1 pathway is closely associated to JNK activation, it is possible that the JNK pathway is also implicated during HCoV-OC43 infection.</p><p>Similar to HCoV infections, it has been shown that the IRE1-XBP1 pathway is activated during IBV infection. Knockdown of IRE1 using specific siRNA in IBV-infected cells augmented IBV-induced apoptosis; however, an opposite effect was observed by XBP1 knockdown in IBV-infected cells. Consistent with the knockdown experiments, transient overexpression of the full-length IRE1α attenuated IBV-induced apoptosis. When both spliced and unspliced forms of XBP1 were overexpressed in IBV-infected cells, the spliced form of XBP1 was shown to be anti-apoptotic and the unspliced form was pro-apoptotic. Overexpression of a dominant-negative XBP1 enhanced IBV-induced apoptosis. Therefore, our findings showed that the anti-apoptotic function of IRE1 during IBV infection could be mediated by its splicing of XBP1, hence converting XBP1 from a pro-apoptotic to anti-apoptotic form. Finally, IRE1 induction during IBV infection was shown to mediate JNK hyperphosphorylation and Akt hypophosphorylation to potentiate the IBV-infected cells to apoptosis [<xref rid="B173-diseases-04-00026" ref-type="bibr">173</xref>].</p></sec></sec><sec id="sec6-diseases-04-00026"><title>6. Human Coronavirus and MAPK Pathways</title><p>The MAPKs are a group of evolutionally conserved serine/theronine kinases that are activated in response to environmental stresses including oxidative stress, DNA damage, cancer development and viral infections [<xref rid="B174-diseases-04-00026" ref-type="bibr">174</xref>,<xref rid="B175-diseases-04-00026" ref-type="bibr">175</xref>,<xref rid="B176-diseases-04-00026" ref-type="bibr">176</xref>]. To date, multiple MAPK pathways have been identified in mammals, and they can be broadly classified into three major categories—the extracellular signal-regulated kinase (ERK), p38 MAPK and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) [<xref rid="B177-diseases-04-00026" ref-type="bibr">177</xref>]. In all MAPK pathways, the signals are transduced downstream via a three-tier protein kinase cascade. In each tier, the kinases are activated by upstream kinases by dual phosphorylation at the Thr-X-Tyr motif (X represents any amino acid). Presence of extracellular stimuli triggers the activation of MAP kinase kinase kinases (MAPKKKs), which then activate the MAP kinase kinases (MAPKKs). These sequential phosphorylation events eventually activate MAPKs which in turn regulate a variety of fundamental cellular processes such as cell proliferation, survival, motility, differentiation, autophagy, apoptosis and regulation of cytokine production (<xref ref-type="fig" rid="diseases-04-00026-f007">Figure 7</xref>) [<xref rid="B178-diseases-04-00026" ref-type="bibr">178</xref>]. </p><sec id="sec6dot1-diseases-04-00026"><title>6.1. Modulation of MAPK Pathways</title><p>Phosphorylation of all three MAPK members has been detected in cells infected with SARS-CoV [<xref rid="B179-diseases-04-00026" ref-type="bibr">179</xref>,<xref rid="B180-diseases-04-00026" ref-type="bibr">180</xref>]. Additionally, the MAPK pathways are also activated during infection by other HCoVs, as discussed below (<xref ref-type="fig" rid="diseases-04-00026-f007">Figure 7</xref>).</p><sec id="sec6dot1dot1-diseases-04-00026"><title>6.1.1. ERK Pathway</title><p>Activation of ERK and its upstream kinases, MEK1/2, was detected in cells infected with SARS-CoV or overexpressed with SARS-CoV S protein [<xref rid="B179-diseases-04-00026" ref-type="bibr">179</xref>,<xref rid="B181-diseases-04-00026" ref-type="bibr">181</xref>]. However, ERK activation did not contribute to phosphorylation of its downstream target, p90 ribosomal S6 kinase (p90RSK) in SARS-CoV-infected Vero E6 cells [<xref rid="B182-diseases-04-00026" ref-type="bibr">182</xref>]. This could be attributed to the higher phosphorylation levels of ERK1 compared to ERK2 in the SARS-CoV-infected cells, as ERK1 has been shown to suppress p90RSK phosphorylation and functional activity [<xref rid="B183-diseases-04-00026" ref-type="bibr">183</xref>]. In another recent study, vimentin, a type III intermediate filament protein, was shown to be critical for entry of SARS-CoV, via direct interaction with the viral S protein [<xref rid="B184-diseases-04-00026" ref-type="bibr">184</xref>]. Since vimentin could associate with β-adrenergic receptor to regulate ERK activation, one could speculate that induction of ERK pathway by SARS-CoV S protein might be through the interaction between vimentin and the ACE2 receptor, which is required for entry of SARS-CoV [<xref rid="B185-diseases-04-00026" ref-type="bibr">185</xref>]. Additionally, binding of SARS-CoV S protein to ACE2 receptor stimulates upregulation of chemokine (C–C motif) ligand 2 (CCL2) mediated by ERK/AP-1 activation. CCL2 is believed to be responsible for respiratory inflammatory symptoms in SARS patients [<xref rid="B181-diseases-04-00026" ref-type="bibr">181</xref>]. SARS-CoV S protein-induced ERK phosphorylation was shown to enhance IL8 release [<xref rid="B186-diseases-04-00026" ref-type="bibr">186</xref>]. Other viral proteins of SARS-CoV have also been shown to induce ERK activation. Expression of SARS-CoV PLpro was shown to increase ERK1 ubiquitin-mediated degradation to suppress IFN-induced responses [<xref rid="B187-diseases-04-00026" ref-type="bibr">187</xref>]. SARS-CoV 3b protein was also involved in ERK phosphorylation to potentiate AP-1 dependent activity of pro-inflammatory cytokine monocyte chemoattractant protein-1 (MCP-1) [<xref rid="B188-diseases-04-00026" ref-type="bibr">188</xref>]. Besides SARS-CoV, MERS-CoV infection is also associated with enhanced ERK phosphorylation profile. The use of ER pathway inhibitor inhibited MERS-CoV infection by approximately 50% [<xref rid="B189-diseases-04-00026" ref-type="bibr">189</xref>]. Although ERK phosphorylation was not significantly affected by HCoV-229E infection, the level of phosphorylated ERK can be enhanced by the use of chloroquine, a known antiviral agent against viruses [<xref rid="B190-diseases-04-00026" ref-type="bibr">190</xref>]. Therefore, targeting the ERK pathway might have significant antiviral potential during HCoV infection.</p></sec><sec id="sec6dot1dot2-diseases-04-00026"><title>6.1.2. JNK Pathway</title><p>Phosphorylation of JNK and its upstream kinases, MKK4/7, was detected in SARS-CoV-infected cells [<xref rid="B191-diseases-04-00026" ref-type="bibr">191</xref>]. Overexpression of SARS-CoV 3a and 7a protein increased JNK activation and augmented IL8 promoter activity [<xref rid="B192-diseases-04-00026" ref-type="bibr">192</xref>]. SARS-CoV 3b protein was shown to induce JNK/c-Jun/AP-1 activation to mediate transcription of MCP-1 [<xref rid="B188-diseases-04-00026" ref-type="bibr">188</xref>]. Concurrently, the S protein of SARS-CoV was also shown to induce the activation of protein kinase epsilon via JNK activation [<xref rid="B193-diseases-04-00026" ref-type="bibr">193</xref>]. Expression of SARS-CoV N protein is associated with the downregulation of prosurvival factors and apoptosis induction in COS-1 cells, possibly mediated by JNK activation [<xref rid="B86-diseases-04-00026" ref-type="bibr">86</xref>]. Apoptosis induced by SARS-CoV 6 and 7a protein in Vero E6 and COS-7 cells were blocked by a JNK inhibitor [<xref rid="B88-diseases-04-00026" ref-type="bibr">88</xref>]. Therefore, these findings suggest that JNK could act as a pro-apoptotic protein during SARS-CoV infection. However, in another study, phosphorylation of JNK was required for the maintenance of Vero E6 cells persistently infected with SARS-CoV. As persistent infection is only established after apoptotic events, it was proposed that JNK might act as a pro-apoptotic during acute phase of infection, but subsequently switched to become anti-apoptotic during prolonged infection [<xref rid="B191-diseases-04-00026" ref-type="bibr">191</xref>]. It is uncertain if these observations noted were dependent on cell-type specificity. In our recent study, our group has found out that JNK was also activated during HCoV-229E infection and serves an anti-apoptotic role via modulation of Bcl2 family proteins. Furthermore, JNK contributes to the production of IFNβ and IL8 in HCoV-229E-infected cells (unpublished). The anti-apoptotic role of JNK during HCoV-229E infection contradicts our observations in H1299 cells infected with animal coronaviruses such as IBV, in which JNK has been shown to be pro-apoptotic [<xref rid="B194-diseases-04-00026" ref-type="bibr">194</xref>]. The discrepancy of the involvement of JNK in CoV infections could be attributed to the different virus strains used in the experiments.</p></sec><sec id="sec6dot1dot3-diseases-04-00026"><title>6.1.3. p38 MAPK Pathway</title><p>Activation of p38 MAPK has been reported in cells infected with SARS-CoV, MERS-CoV and HCoV-229E [<xref rid="B180-diseases-04-00026" ref-type="bibr">180</xref>,<xref rid="B189-diseases-04-00026" ref-type="bibr">189</xref>,<xref rid="B190-diseases-04-00026" ref-type="bibr">190</xref>]. The upstream kinases of p38 MAPK, MKK3/6 were also shown to be phosphorylated [<xref rid="B179-diseases-04-00026" ref-type="bibr">179</xref>]. On the other hand, downstream effectors of p38, MAPK-activated protein kinase-2 (MAPKAPK-2), cAMP response element-binding protein (CREB) and activation transcription factor-1 (ATF-1), were also activated in SARS-CoV-infected cells. SARS-CoV-induced phosphorylation of eukaryotic initiation factor 4E (eIF4a) was attenuated by p38 MAPK inhibitor. Although eIF4a is involved in protein translation, SARS-CoV viral protein translation and viral replication was not attenuated by p38 MAPK inhibitor, suggesting that SARS-CoV did not ultilise p38 for viral protein synthesis [<xref rid="B180-diseases-04-00026" ref-type="bibr">180</xref>]. Furthermore, SARS-CoV infection induced p90RSK Ser380 phosphorylation, which could be partially negated by p38 MAPK inhibitor. Analysis of individual SARS-CoV proteins demonstrated that transfection of its 7a protein induced p38 activation when fused with GFP [<xref rid="B195-diseases-04-00026" ref-type="bibr">195</xref>]. Since SARS-CoV 7a and 3a protein co-immunoprecipitated, they are likely to co-interact in virus-infected cells [<xref rid="B196-diseases-04-00026" ref-type="bibr">196</xref>]. Therefore, it is possible that simultaneous co-expression of 7a and 3a proteins might further enhance p38 phosphorylation. In a recent study, the PBZ-binding motif (PBM) of SARS-CoV E protein was demonstrated to bind to syntenin and redistributes it to the cytoplasm, where it acts as a major scaffolding protein for p38 signalling cascade. Inhibition of syntenin using specific siRNA in cells transfected with functional E protein led to decreased p38 MAPK signalling [<xref rid="B197-diseases-04-00026" ref-type="bibr">197</xref>]. Consistent with cell culture studies, phosphorylated p38 MAPK level was found to be increased in leukocytes of SARS patients. Enhanced p38, but not ERK, activation likely contributes to elevated IL8 levels and abnormal cytokine profile in SARS patients [<xref rid="B198-diseases-04-00026" ref-type="bibr">198</xref>]. Additionally, p38 might also be involved in HCoV replication, as exemplified by HCoV-229E. Inhibition of p38 by its inhibitor SB203580 suppressed the HCoV-229E-induced cytopathic effects and significantly reduced viral titres in a dose dependent manner [<xref rid="B190-diseases-04-00026" ref-type="bibr">190</xref>]. The use of chloroquine was also shown to exert antiviral effects against HCoV-229E infection, possibly via its attenuation on p38 activation [<xref rid="B190-diseases-04-00026" ref-type="bibr">190</xref>].</p></sec></sec></sec><sec id="sec7-diseases-04-00026"><title>7. Human Coronavirus and NF-κB Pathway</title><p>The NF-κB proteins are a family of transcription factors that regulate expression of genes to control a broad range of biological processes, such as cell death, inflammation, innate and adaptive immune responses. Mammalian NF-κB family composes of five members, RelA (also named p65), RelB, c-Rel, NF-κB1 p50, and NF-κB2 p52, which form dimers in the cytoplasm. It has been established that NF-κB pathway is often targeted by viral pathogens to enhance viral replication, host cell survival and host immune evasion [<xref rid="B199-diseases-04-00026" ref-type="bibr">199</xref>,<xref rid="B200-diseases-04-00026" ref-type="bibr">200</xref>]. There are two main pathways for NF-κB signalling—the canonical and non-canonical pathways. </p><p>In the canonical pathway, the latent NF-κB forms a complex with its inhibitor IκB protein and is sequestered in the cytoplasm. As mentioned above, presence of viral pathogens activate various membrane sensors such as RIG-I, which induces the phosphorylation IκB by IκB kinase (IKK) complex and its subsequent ubiquitination. IKK complex consists of trimeric subunits including two catalytic subunits, IKKα and IKKβ, and a regulatory subunit, IKKγ (also named NF-κB essential modulator or NEMO). NF-κB is thus released from the inhibitory effects of IκB and translocates to the nucleus, where it stimulates transcription of target genes, either alone or in combination with other transcription factors including AP-1, Ets, and Stat [<xref rid="B201-diseases-04-00026" ref-type="bibr">201</xref>]. On the other hand, the non-canonical pathway is independent of IκB degradation, but instead relies on inducible p100 processing. Activation of NF-κB inducing kinase (NIK), a MAPKKK, induces the phosphorylation and activation of IKKα dimeric complex, in turn activating p100. This results in the release of p52/RelB heterodimer from sequestration by p100. The p52/RelB heterodimer translocates to the nucleus to activate target genes related to a number of cellular functions, in particularly cell proliferation, survival and innate immunity [<xref rid="B202-diseases-04-00026" ref-type="bibr">202</xref>].</p><sec id="sec7dot1-diseases-04-00026"><title>7.1. Modulation of NF-κB Pathway</title><p>NF-κB pathway has been shown to play an important role in HCoV infections. NF-κB was activated in lungs of mice infected with recombinant SARS-CoV [<xref rid="B203-diseases-04-00026" ref-type="bibr">203</xref>]. In the same study, however, subsequent treatment of these infected lung cells with NF-κB inhibitors did not affect virus titres but reduce expression of TNF, CCL2 and CXCL2, hence suggesting that NF-κB is essential for SARS-CoV-mediated induction of pro-inflammatory cytokines [<xref rid="B203-diseases-04-00026" ref-type="bibr">203</xref>]. HCoV-229E was also shown to mediate IL8 induction in peripheral blood mononuclear cells (PBMC), which could be attenuated by NF-κB inhibitor [<xref rid="B204-diseases-04-00026" ref-type="bibr">204</xref>]. Modulation of NF-κB is mediated via several viral proteins of HCoVs (<xref ref-type="fig" rid="diseases-04-00026-f005">Figure 5</xref>).</p><sec id="sec7dot1dot1-diseases-04-00026"><title>7.1.1. Structural Proteins</title><p>In SARS-CoV, the S, M, E and N structural proteins have been demonstrated to interfere with NF-κB signalling. A recent study reported an enhanced nuclear NF-κB activity in PBMCs treated with a purified and recombinant SARS-CoV S protein. Synthesis and secretion of IL8 in these S protein-treated cells could be suppressed by NF-κB inhibitor, hence suggesting that NF-κB regulates pro-inflammatory cytokine levels in these cells [<xref rid="B204-diseases-04-00026" ref-type="bibr">204</xref>]. SARS-CoV S protein likely stimulates NF-κB via the upregulation of an upstream protein kinase C (PKC) isozyme PKCα, since S activated ERK and JNK were PKC dependent [<xref rid="B192-diseases-04-00026" ref-type="bibr">192</xref>]. Although IL8 synthesis and secretion was not promoted by SARS-CoV E protein [<xref rid="B204-diseases-04-00026" ref-type="bibr">204</xref>], deletion of E protein in recombinant SARS-CoV reduced NF-κB activation [<xref rid="B203-diseases-04-00026" ref-type="bibr">203</xref>]. Additionally, overexpression of SARS-CoV N protein significantly increased NF-κB luciferase activity in a dose-dependent manner in Vero E6 cells, but not Vero, HeLa and Huh-7 cells, suggesting that this induction of NF-κB might be cell-specific [<xref rid="B205-diseases-04-00026" ref-type="bibr">205</xref>,<xref rid="B206-diseases-04-00026" ref-type="bibr">206</xref>]. On the other hand, co-immunoprecipitation experiments showed that SARS-CoV M protein physically bind to IKKb to sequester it in the cytoplasm, hence inhibiting the activation of NF-κB [<xref rid="B207-diseases-04-00026" ref-type="bibr">207</xref>]. However, the MERS-CoV M protein did not affect the luciferase activity controlled by a promoter with NF-κB binding sites, although we cannot rule out the possibility that some other structural or non-structural MERS-CoV protein might be involved [<xref rid="B133-diseases-04-00026" ref-type="bibr">133</xref>]. For HCoV-OC43, expression of its N protein alone was unable to activate NF-κB, unless under the stimulation of TNFα. This potentiation of NF-κB activation was through the interaction between HCoV-OC43 N and microRNA 9, which inhibits NF-κB [<xref rid="B208-diseases-04-00026" ref-type="bibr">208</xref>].</p></sec><sec id="sec7dot1dot2-diseases-04-00026"><title>7.1.2. Nonstructural and Accessory Proteins</title><p>Previously, it was demonstrated that overexpression of SARS-CoV nsp1, but not HCoV-229E nsp1, could induce NF-κB activation [<xref rid="B138-diseases-04-00026" ref-type="bibr">138</xref>]. The use of NF-κB inhibitor suppressed SARS-CoV nsp1-induced chemokine expression in a dose-dependent manner [<xref rid="B209-diseases-04-00026" ref-type="bibr">209</xref>]. The PLpro domain found within nsp3 of SARS-CoV and MERS-CoV was shown to antagonize IFN and NF-κB activities [<xref rid="B139-diseases-04-00026" ref-type="bibr">139</xref>,<xref rid="B210-diseases-04-00026" ref-type="bibr">210</xref>]. However, in another study, SARS-CoV PLpro domain did not significantly negate the induction of expression of NFκB-dependent genes by Sendai virus infection [<xref rid="B140-diseases-04-00026" ref-type="bibr">140</xref>]. Nevertheless, it was shown that SARS-CoV PLpro repressed NF-κB activation by removing K48-linked ubiquitination from IκBα [<xref rid="B211-diseases-04-00026" ref-type="bibr">211</xref>].</p><p>Other accessory proteins of HCoVs have also been shown to interfere with NF-κB signalling. Expression of SARS-CoV 3a and 7a proteins was shown to significantly induce NF-κB-dependent luciferase activity. Enhancement of IL8 promoter activity by SARS-CoV 3a and 7a protein was negated by mutating the NF-κB binding site on the promoter [<xref rid="B192-diseases-04-00026" ref-type="bibr">192</xref>]. Previously, expression of MERS-CoV ORF4a, but not ORF4b and ORF5, was shown to inhibit Sendai virus-induced firefly luciferase activity under the control of a NFκB-responsive promoter [<xref rid="B133-diseases-04-00026" ref-type="bibr">133</xref>]. However, in another study, MERS-CoV ORF4b was demonstrated to moderately attenuate NF-κB-dependent luciferase activity induced upon TNFα treatment [<xref rid="B212-diseases-04-00026" ref-type="bibr">212</xref>].</p></sec></sec></sec><sec id="sec8-diseases-04-00026"><title>8. Conclusions</title><p>The relationship between a virus and its host is a complicated affair: a myriad of factors from the virus and the host are involved in viral infection and consequential pathogenesis. During viral infections, the host must respond to the virus by putting multiple lines of defence mechanisms in place. As intracellular obligate parasites, viruses have also evolved various strategies to hijack the host machineries. In this review, we first showed how viral factors could manipulate the host cell to expedite its own replication cycle and pathogenesis. We also highlighted how multiple cellular and viral factors come into play in their long-standing battle against one another. </p><p>For years, HCoVs have been identified as mild respiratory pathogens that affect the human population. However, it was the emergence of SARS-CoV that thrust these human viruses into the spotlight of the research field. Therefore, most of the HCoV research today is pertained towards SARS-CoV. While the recent MERS-CoV outbreak has been mostly limited to the Middle East region, it is likely that more emerging or re-emerging HCoVs might surface to threaten the global public health, as seen from the high mortality rates in the past two outbreaks: SARS-CoV (10%) and MERS-CoV (35%). Therefore, study of the pathogenesis of all HCoVs would gain more insights for the development of antiviral therapeutics and vaccines.</p></sec></body><back><ack><title>Acknowledgments</title><p>This work was partially supported by a Competitive Research Programme (CRP) grant (NRF-CRP8-2011-05), the National Research Foundation, Singapore, an Academic Research Fund (AcRF) Tier 1 grant (RGT17/13), Nanyang Technological University and Ministry of Education, Singapore, and an AcRF Tier 2 grant (ACR47/14), Ministry of Education, Singapore.</p></ack><notes><title>Author Contributions</title><p>Yvonne Xinyi Lim and Yan Ling Ng wrote the paper; and James P. Tam and Ding Xiang Liu revised the manuscript. </p></notes><notes notes-type="COI-statement"><title>Conflicts of Interest</title><p>The authors declare no conflict of interest.</p></notes><ref-list><title>References</title><ref id="B1-diseases-04-00026"><label>1.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pene</surname><given-names>F.</given-names></name><name><surname>Merlat</surname><given-names>A.</given-names></name><name><surname>Vabret</surname><given-names>A.</given-names></name><name><surname>Rozenberg</surname><given-names>F.</given-names></name><name><surname>Buzyn</surname><given-names>A.</given-names></name><name><surname>Dreyfus</surname><given-names>F.</given-names></name><name><surname>Cariou</surname><given-names>A.</given-names></name><name><surname>Freymuth</surname><given-names>F.</given-names></name><name><surname>Lebon</surname><given-names>P.</given-names></name></person-group><article-title>Coronavirus 229E-Related Pneumonia in Immunocompromised Patients</article-title><source>Clin. Infect. Dis.</source><year>2003</year><volume>37</volume><fpage>929</fpage><lpage>932</lpage><pub-id pub-id-type="doi">10.1086/377612</pub-id><pub-id pub-id-type="pmid">13130404</pub-id></element-citation></ref><ref id="B2-diseases-04-00026"><label>2.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vijgen</surname><given-names>L.</given-names></name><name><surname>Keyaerts</surname><given-names>E.</given-names></name><name><surname>Moës</surname><given-names>E.</given-names></name><name><surname>Maes</surname><given-names>P.</given-names></name><name><surname>Duson</surname><given-names>G.</given-names></name><name><surname>van Ranst</surname><given-names>M.</given-names></name></person-group><article-title>Development of One-Step, Real-Time, Quantitative Reverse Transcriptase PCR Assays for Absolute Quantitation of Human Coronaviruses OC43 and 229E</article-title><source>J. Clin. Microbiol.</source><year>2005</year><volume>43</volume><fpage>5452</fpage><lpage>5456</lpage><pub-id pub-id-type="doi">10.1128/JCM.43.11.5452-5456.2005</pub-id><pub-id pub-id-type="pmid">16272469</pub-id></element-citation></ref><ref id="B3-diseases-04-00026"><label>3.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jones</surname><given-names>B.A.</given-names></name><name><surname>Grace</surname><given-names>D.</given-names></name><name><surname>Kock</surname><given-names>R.</given-names></name><name><surname>Alonso</surname><given-names>S.</given-names></name><name><surname>Rushton</surname><given-names>J.</given-names></name><name><surname>Said</surname><given-names>M.Y.</given-names></name><name><surname>McKeever</surname><given-names>D.</given-names></name><name><surname>Mutua</surname><given-names>F.</given-names></name><name><surname>Young</surname><given-names>J.</given-names></name><name><surname>McDermott</surname><given-names>J.</given-names></name><etal></etal></person-group><article-title>Zoonosis emergence linked to agricultural intensification and environmental change</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2013</year><volume>21</volume><fpage>8399</fpage><lpage>8340</lpage><pub-id pub-id-type="doi">10.1073/pnas.1208059110</pub-id><pub-id pub-id-type="pmid">23671097</pub-id></element-citation></ref><ref id="B4-diseases-04-00026"><label>4.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Van der Hoek</surname><given-names>L.</given-names></name></person-group><article-title>Human coronaviruses: What do they cause?</article-title><source>Antivir. Ther.</source><year>2007</year><volume>12</volume><fpage>651</fpage><lpage>658</lpage><pub-id pub-id-type="pmid">17944272</pub-id></element-citation></ref><ref id="B5-diseases-04-00026"><label>5.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Walsh 2007</surname><given-names>E.E.</given-names></name><name><surname>Shin</surname><given-names>J.H.</given-names></name><name><surname>Falsey</surname><given-names>A.R.</given-names></name></person-group><article-title>Clinical Impact of Human Coronaviruses 229E and OC43 Infection in Diverse Adult Populations</article-title><source>J. Infect. Dis.</source><year>2013</year><volume>208</volume><fpage>1634</fpage><lpage>1642</lpage><pub-id pub-id-type="doi">10.1093/infdis/jit393</pub-id><pub-id pub-id-type="pmid">23922367</pub-id></element-citation></ref><ref id="B6-diseases-04-00026"><label>6.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gorse</surname><given-names>G.J.</given-names></name><name><surname>O’Connor</surname><given-names>T.Z.</given-names></name><name><surname>Hall</surname><given-names>S.L.</given-names></name><name><surname>Vitale</surname><given-names>J.N.</given-names></name><name><surname>Nichol</surname><given-names>K.L.</given-names></name></person-group><article-title>Human Coronavirus and Acute Respiratory Illness in Older Adults with Chronic Obstructive Pulmonary Disease</article-title><source>J. Infect. Dis.</source><year>2009</year><volume>199</volume><fpage>847</fpage><lpage>857</lpage><pub-id pub-id-type="doi">10.1086/597122</pub-id><pub-id pub-id-type="pmid">19239338</pub-id></element-citation></ref><ref id="B7-diseases-04-00026"><label>7.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arbour</surname><given-names>N.</given-names></name><name><surname>Day</surname><given-names>R.</given-names></name><name><surname>Newcombe</surname><given-names>J.</given-names></name><name><surname>Talbot</surname><given-names>P.J.</given-names></name></person-group><article-title>Neuroinvasion by Human Respiratory Coronaviruses</article-title><source>J. Virol.</source><year>2000</year><volume>74</volume><fpage>8913</fpage><lpage>8921</lpage><pub-id pub-id-type="doi">10.1128/JVI.74.19.8913-8921.2000</pub-id><pub-id pub-id-type="pmid">10982334</pub-id></element-citation></ref><ref id="B8-diseases-04-00026"><label>8.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arbour</surname><given-names>N.</given-names></name><name><surname>Ekandé</surname><given-names>S.</given-names></name><name><surname>Côté</surname><given-names>G.</given-names></name><name><surname>Lachance</surname><given-names>C.</given-names></name><name><surname>Chagnon</surname><given-names>F.</given-names></name><name><surname>Tardieu</surname><given-names>M.</given-names></name><name><surname>Cashman</surname><given-names>N.R.</given-names></name><name><surname>Talbot</surname><given-names>P.J.</given-names></name></person-group><article-title>Persistent Infection of Human Oligodendrocytic and Neuroglial Cell Lines by Human Coronavirus 229E</article-title><source>J. Virol.</source><year>1999</year><volume>73</volume><fpage>3326</fpage><lpage>3337</lpage><pub-id pub-id-type="pmid">10074187</pub-id></element-citation></ref><ref id="B9-diseases-04-00026"><label>9.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jacomy</surname><given-names>H.</given-names></name><name><surname>Fragoso</surname><given-names>G.</given-names></name><name><surname>Almazan</surname><given-names>G.</given-names></name><name><surname>Mushynski</surname><given-names>W.E.</given-names></name><name><surname>Talbot</surname><given-names>P.J.</given-names></name></person-group><article-title>Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice</article-title><source>Virology</source><year>2006</year><volume>349</volume><fpage>335</fpage><lpage>346</lpage><pub-id pub-id-type="doi">10.1016/j.virol.2006.01.049</pub-id><pub-id pub-id-type="pmid">16527322</pub-id></element-citation></ref><ref id="B10-diseases-04-00026"><label>10.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vabret</surname><given-names>A.</given-names></name><name><surname>Mourez</surname><given-names>T.</given-names></name><name><surname>Gouarin</surname><given-names>S.</given-names></name><name><surname>Petitjean</surname><given-names>J.</given-names></name><name><surname>Freymuth</surname><given-names>F.</given-names></name></person-group><article-title>An Outbreak of Coronavirus OC43 Respiratory Infection in Normandy, France</article-title><source>Clin. Infect. Dis.</source><year>2003</year><volume>36</volume><fpage>985</fpage><lpage>989</lpage><pub-id pub-id-type="doi">10.1086/374222</pub-id><pub-id pub-id-type="pmid">12684910</pub-id></element-citation></ref><ref id="B11-diseases-04-00026"><label>11.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Smuts</surname><given-names>H.</given-names></name></person-group><article-title>Human coronavirus NL63 infections in infants hospitalised with acute respiratory tract infections in South Africa</article-title><source>Influenza Other Respir. Viruses</source><year>2008</year><volume>2</volume><fpage>135</fpage><lpage>138</lpage><pub-id pub-id-type="doi">10.1111/j.1750-2659.2008.00049.x</pub-id><pub-id pub-id-type="pmid">19453465</pub-id></element-citation></ref><ref id="B12-diseases-04-00026"><label>12.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Graham</surname><given-names>R.L.</given-names></name><name><surname>Donaldson</surname><given-names>E.F.</given-names></name><name><surname>Baric</surname><given-names>R.S.</given-names></name></person-group><article-title>A decade after SARS: Strategies for controlling emerging coronaviruses</article-title><source>Nat. Rev. Microbiol.</source><year>2013</year><volume>11</volume><fpage>836</fpage><lpage>848</lpage><pub-id pub-id-type="doi">10.1038/nrmicro3143</pub-id><pub-id pub-id-type="pmid">24217413</pub-id></element-citation></ref><ref id="B13-diseases-04-00026"><label>13.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Frieman</surname><given-names>M.</given-names></name><name><surname>Baric</surname><given-names>R.</given-names></name></person-group><article-title>Mechanisms of Severe Acute Respiratory Syndrome Pathogenesis and Innate Immunomodulation</article-title><source>Microbiol. Mol. Biol. Rev. MMBR</source><year>2008</year><volume>72</volume><fpage>672</fpage><lpage>685</lpage><pub-id pub-id-type="doi">10.1128/MMBR.00015-08</pub-id><pub-id pub-id-type="pmid">19052324</pub-id></element-citation></ref><ref id="B14-diseases-04-00026"><label>14.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Peiris</surname><given-names>J.S.M.</given-names></name><name><surname>Guan</surname><given-names>Y.</given-names></name><name><surname>Yuen</surname><given-names>K.Y.</given-names></name></person-group><article-title>Severe acute respiratory syndrome</article-title><source>Nat. Med.</source><year>2004</year><volume>10</volume><fpage>S88</fpage><lpage>S97</lpage><pub-id pub-id-type="doi">10.1038/nm1143</pub-id><pub-id pub-id-type="pmid">15577937</pub-id></element-citation></ref><ref id="B15-diseases-04-00026"><label>15.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>M.</given-names></name><name><surname>Yan</surname><given-names>M.</given-names></name><name><surname>Xu</surname><given-names>H.</given-names></name><name><surname>Liang</surname><given-names>W.</given-names></name><name><surname>Kan</surname><given-names>B.</given-names></name><name><surname>Zheng</surname><given-names>B.</given-names></name><name><surname>Chen</surname><given-names>H.</given-names></name><name><surname>Zheng</surname><given-names>H.</given-names></name><name><surname>Xu</surname><given-names>Y.</given-names></name><name><surname>Zhang</surname><given-names>E.</given-names></name><etal></etal></person-group><article-title>SARS-CoV Infection in a Restaurant from Palm Civet</article-title><source>Emerg. Infect. Dis.</source><year>2005</year><volume>11</volume><fpage>1860</fpage><lpage>1865</lpage><pub-id pub-id-type="doi">10.3201/eid1112.041293</pub-id><pub-id pub-id-type="pmid">16485471</pub-id></element-citation></ref><ref id="B16-diseases-04-00026"><label>16.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hu</surname><given-names>B.</given-names></name><name><surname>Ge</surname><given-names>X.</given-names></name><name><surname>Wang</surname><given-names>L.-F.</given-names></name><name><surname>Shi</surname><given-names>Z.</given-names></name></person-group><article-title>Bat origin of human coronaviruses</article-title><source>Virol. J.</source><year>2015</year><volume>12</volume><fpage>221</fpage><pub-id pub-id-type="doi">10.1186/s12985-015-0422-1</pub-id><pub-id pub-id-type="pmid">26689940</pub-id></element-citation></ref><ref id="B17-diseases-04-00026"><label>17.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>Y.</given-names></name><name><surname>Cheon</surname><given-names>S.</given-names></name><name><surname>Min</surname><given-names>C.-K.</given-names></name><name><surname>Sohn</surname><given-names>K.M.</given-names></name><name><surname>Kang</surname><given-names>Y.J.</given-names></name><name><surname>Cha</surname><given-names>Y.-J.</given-names></name><name><surname>Kang</surname><given-names>J.I.</given-names></name><name><surname>Han</surname><given-names>S.K.</given-names></name><name><surname>Ha</surname><given-names>N.Y.</given-names></name><name><surname>Kim</surname><given-names>G.</given-names></name><etal></etal></person-group><article-title>Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak</article-title><source>mBio</source><year>2016</year><volume>7</volume><pub-id pub-id-type="doi">10.1128/mBio.00019-16</pub-id><pub-id pub-id-type="pmid">26933050</pub-id></element-citation></ref><ref id="B18-diseases-04-00026"><label>18.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oboho</surname><given-names>I.K.</given-names></name><name><surname>Tomczyk</surname><given-names>S.M.</given-names></name><name><surname>Al-Asmari</surname><given-names>A.M.</given-names></name><name><surname>Banjar</surname><given-names>A.A.</given-names></name><name><surname>Al-Mugti</surname><given-names>H.</given-names></name><name><surname>Aloraini</surname><given-names>M.S.</given-names></name><name><surname>Alkhaldi</surname><given-names>K.Z.</given-names></name><name><surname>Almohammadi</surname><given-names>E.L.</given-names></name><name><surname>Alraddadi</surname><given-names>B.M.</given-names></name><name><surname>Gerber</surname><given-names>S.I.</given-names></name><etal></etal></person-group><article-title>2014 MERS-CoV Outbreak in Jeddah—A Link to Health Care Facilities</article-title><source>N. Engl. J. Med.</source><year>2015</year><volume>372</volume><fpage>846</fpage><lpage>854</lpage><pub-id pub-id-type="doi">10.1056/NEJMoa1408636</pub-id><pub-id pub-id-type="pmid">25714162</pub-id></element-citation></ref><ref id="B19-diseases-04-00026"><label>19.</label><element-citation publication-type="journal"><person-group person-group-type="author"><collab>The Korean Society of Infectious Diseases; Korean Society for Healthcare-associated Infection Control and Prevention</collab></person-group><article-title>An Unexpected Outbreak of Middle East Respiratory Syndrome Coronavirus Infection in the Republic of Korea, 2015</article-title><source>Infect. Chemother.</source><year>2015</year><volume>47</volume><fpage>120</fpage><lpage>122</lpage><pub-id pub-id-type="pmid">26157591</pub-id></element-citation></ref><ref id="B20-diseases-04-00026"><label>20.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Masters</surname><given-names>P.S.</given-names></name></person-group><source>The Molecular Biology of Coronaviruses Advances in Virus Research</source><publisher-name>Academic Press</publisher-name><publisher-loc>Massachusetts, MA, USA</publisher-loc><year>2006</year><volume>Volume 66</volume><fpage>193</fpage><lpage>292</lpage></element-citation></ref><ref id="B21-diseases-04-00026"><label>21.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McBride</surname><given-names>R.</given-names></name><name><surname>Fielding</surname><given-names>B.C.</given-names></name></person-group><article-title>The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis</article-title><source>Viruses</source><year>2012</year><volume>4</volume><fpage>2902</fpage><lpage>2923</lpage><pub-id pub-id-type="doi">10.3390/v4112902</pub-id><pub-id pub-id-type="pmid">23202509</pub-id></element-citation></ref><ref id="B22-diseases-04-00026"><label>22.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gorbalenya</surname><given-names>A.E.</given-names></name><name><surname>Snijder</surname><given-names>E.J.</given-names></name><name><surname>Spaan</surname><given-names>W.J.M.</given-names></name></person-group><article-title>Severe Acute Respiratory Syndrome Coronavirus Phylogeny: Toward Consensus</article-title><source>J. Virol.</source><year>2004</year><volume>78</volume><fpage>7863</fpage><lpage>7866</lpage><pub-id pub-id-type="doi">10.1128/JVI.78.15.7863-7866.2004</pub-id><pub-id pub-id-type="pmid">15254158</pub-id></element-citation></ref><ref id="B23-diseases-04-00026"><label>23.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kolesnikova</surname><given-names>L.</given-names></name><name><surname>Slenczka</surname><given-names>W.</given-names></name><name><surname>Brodt</surname><given-names>H.</given-names></name><name><surname>Klenk</surname><given-names>H.</given-names></name><name><surname>Becker</surname><given-names>S.</given-names></name></person-group><article-title>Electron microscopy in diagnostics of SARS case</article-title><source>Microsc. Microanal.</source><year>2003</year><volume>9</volume><fpage>438</fpage><lpage>439</lpage></element-citation></ref><ref id="B24-diseases-04-00026"><label>24.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marsolais</surname><given-names>G.</given-names></name><name><surname>Berthiaume</surname><given-names>L.</given-names></name><name><surname>DiFranco</surname><given-names>E.</given-names></name><name><surname>Marois</surname><given-names>P.</given-names></name></person-group><article-title>Rapid Diagnosis by Electron Microscopy of Avian Coronavirus Infection</article-title><source>Can. J. Comp. Med.</source><year>1971</year><volume>35</volume><fpage>285</fpage><lpage>288</lpage><pub-id pub-id-type="pmid">4260941</pub-id></element-citation></ref><ref id="B25-diseases-04-00026"><label>25.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>D.X.</given-names></name><name><surname>Fung</surname><given-names>T.S.</given-names></name><name><surname>Chong</surname><given-names>K.K.-L.</given-names></name><name><surname>Shukla</surname><given-names>A.</given-names></name><name><surname>Hilgenfeld</surname><given-names>R.</given-names></name></person-group><article-title>Accessory proteins of SARS-CoV and other coronaviruses</article-title><source>Antivir. Res.</source><year>2014</year><volume>109</volume><fpage>97</fpage><lpage>109</lpage><pub-id pub-id-type="doi">10.1016/j.antiviral.2014.06.013</pub-id><pub-id pub-id-type="pmid">24995382</pub-id></element-citation></ref><ref id="B26-diseases-04-00026"><label>26.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yeager</surname><given-names>C.L.</given-names></name><name><surname>Ashmun</surname><given-names>R.A.</given-names></name><name><surname>Williams</surname><given-names>R.K.</given-names></name><name><surname>Cardellichio</surname><given-names>C.B.</given-names></name><name><surname>Shapiro</surname><given-names>L.H.</given-names></name><name><surname>Look</surname><given-names>A.T.</given-names></name><name><surname>Holmes</surname><given-names>K.V.</given-names></name></person-group><article-title>Human aminopeptidase N is a receptor for human coronavirus 229E</article-title><source>Nature</source><year>1992</year><volume>357</volume><fpage>420</fpage><lpage>422</lpage><pub-id pub-id-type="doi">10.1038/357420a0</pub-id><pub-id pub-id-type="pmid">1350662</pub-id></element-citation></ref><ref id="B27-diseases-04-00026"><label>27.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Moore</surname><given-names>M.J.</given-names></name><name><surname>Vasilieva</surname><given-names>N.</given-names></name><name><surname>Sui</surname><given-names>J.</given-names></name><name><surname>Wong</surname><given-names>S.K.</given-names></name><name><surname>Berne</surname><given-names>M.A.</given-names></name><name><surname>Somasundaran</surname><given-names>M.</given-names></name><name><surname>Sullivan</surname><given-names>J.L.</given-names></name><name><surname>Luzuriaga</surname><given-names>K.</given-names></name><name><surname>Greenough</surname><given-names>T.C.</given-names></name><etal></etal></person-group><article-title>Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus</article-title><source>Nature</source><year>2003</year><volume>426</volume><fpage>450</fpage><lpage>454</lpage><pub-id pub-id-type="doi">10.1038/nature02145</pub-id><pub-id pub-id-type="pmid">14647384</pub-id></element-citation></ref><ref id="B28-diseases-04-00026"><label>28.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Sui</surname><given-names>J.</given-names></name><name><surname>Huang</surname><given-names>I.C.</given-names></name><name><surname>Kuhn</surname><given-names>J.H.</given-names></name><name><surname>Radoshitzky</surname><given-names>S.R.</given-names></name><name><surname>Marasco</surname><given-names>W.A.</given-names></name><name><surname>Choe</surname><given-names>H.</given-names></name><name><surname>Farzan</surname><given-names>M.</given-names></name></person-group><article-title>The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2</article-title><source>Virology</source><year>2007</year><volume>367</volume><fpage>367</fpage><lpage>374</lpage><pub-id pub-id-type="doi">10.1016/j.virol.2007.04.035</pub-id><pub-id pub-id-type="pmid">17631932</pub-id></element-citation></ref><ref id="B29-diseases-04-00026"><label>29.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wu</surname><given-names>K.</given-names></name><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Peng</surname><given-names>G.</given-names></name><name><surname>Li</surname><given-names>F.</given-names></name></person-group><article-title>Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2009</year><volume>106</volume><fpage>19970</fpage><lpage>19974</lpage><pub-id pub-id-type="doi">10.1073/pnas.0908837106</pub-id><pub-id pub-id-type="pmid">19901337</pub-id></element-citation></ref><ref id="B30-diseases-04-00026"><label>30.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Van Doremalen</surname><given-names>N.</given-names></name><name><surname>Miazgowicz</surname><given-names>K.L.</given-names></name><name><surname>Milne-Price</surname><given-names>S.</given-names></name><name><surname>Bushmaker</surname><given-names>T.</given-names></name><name><surname>Robertson</surname><given-names>S.</given-names></name><name><surname>Scott</surname><given-names>D.</given-names></name><name><surname>Kinne</surname><given-names>J.</given-names></name><name><surname>McLellan</surname><given-names>J.S.</given-names></name><name><surname>Zhu</surname><given-names>J.</given-names></name><name><surname>Munster</surname><given-names>V.J.</given-names></name></person-group><article-title>Host Species Restriction of Middle East Respiratory Syndrome Coronavirus through Its Receptor, Dipeptidyl Peptidase 4</article-title><source>J. Virol.</source><year>2014</year><volume>88</volume><fpage>9220</fpage><lpage>9232</lpage><pub-id pub-id-type="doi">10.1128/JVI.00676-14</pub-id><pub-id pub-id-type="pmid">24899185</pub-id></element-citation></ref><ref id="B31-diseases-04-00026"><label>31.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>X.</given-names></name><name><surname>Dong</surname><given-names>W.</given-names></name><name><surname>Milewska</surname><given-names>A.</given-names></name><name><surname>Golda</surname><given-names>A.</given-names></name><name><surname>Qi</surname><given-names>Y.</given-names></name><name><surname>Zhu</surname><given-names>Q.K.</given-names></name><name><surname>Marasco</surname><given-names>W.A.</given-names></name><name><surname>Baric</surname><given-names>R.S.</given-names></name><name><surname>Sims</surname><given-names>A.C.</given-names></name><name><surname>Pyrc</surname><given-names>K.</given-names></name><etal></etal></person-group><article-title>Human Coronavirus HKU1 Spike Protein Uses O-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme</article-title><source>J. Virol.</source><year>2015</year><volume>89</volume><fpage>7202</fpage><lpage>7213</lpage><pub-id pub-id-type="doi">10.1128/JVI.00854-15</pub-id><pub-id pub-id-type="pmid">25926653</pub-id></element-citation></ref><ref id="B32-diseases-04-00026"><label>32.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Butler</surname><given-names>N.</given-names></name><name><surname>Pewe</surname><given-names>L.</given-names></name><name><surname>Trandem</surname><given-names>K.</given-names></name><name><surname>Perlman</surname><given-names>S.</given-names></name></person-group><article-title>Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated</article-title><source>Virology</source><year>2006</year><volume>347</volume><fpage>410</fpage><lpage>421</lpage><pub-id pub-id-type="doi">10.1016/j.virol.2005.11.044</pub-id><pub-id pub-id-type="pmid">16413043</pub-id></element-citation></ref><ref id="B33-diseases-04-00026"><label>33.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zumla</surname><given-names>A.</given-names></name><name><surname>Chan</surname><given-names>J.W.</given-names></name><name><surname>Azhar</surname><given-names>E.I.</given-names></name><name><surname>Hui</surname><given-names>D.C.</given-names></name><name><surname>Yuen</surname><given-names>K.</given-names></name></person-group><article-title>Coronaviruses—Drug discovery and therapeutic options</article-title><source>Nat. Rev. Drug Discov.</source><year>2016</year><volume>15</volume><fpage>327</fpage><lpage>347</lpage><pub-id pub-id-type="doi">10.1038/nrd.2015.37</pub-id><pub-id pub-id-type="pmid">26868298</pub-id></element-citation></ref><ref id="B34-diseases-04-00026"><label>34.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bosch</surname><given-names>B.J.</given-names></name><name><surname>Bartelink</surname><given-names>W.</given-names></name><name><surname>Rottier</surname><given-names>P.J.M.</given-names></name></person-group><article-title>Cathepsin L Functionally Cleaves the Severe Acute Respiratory Syndrome Coronavirus Class I Fusion Protein Upstream of Rather than Adjacent to the Fusion Peptide</article-title><source>J. Virol.</source><year>2008</year><volume>82</volume><fpage>8887</fpage><lpage>8890</lpage><pub-id pub-id-type="doi">10.1128/JVI.00415-08</pub-id><pub-id pub-id-type="pmid">18562523</pub-id></element-citation></ref><ref id="B35-diseases-04-00026"><label>35.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Qian</surname><given-names>Z.</given-names></name><name><surname>Dominguez</surname><given-names>S.R.</given-names></name><name><surname>Holmes</surname><given-names>K.V.</given-names></name></person-group><article-title>Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia Formation</article-title><source>PLoS ONE</source><year>2013</year><volume>8</volume><elocation-id>e76469</elocation-id><pub-id pub-id-type="doi">10.1371/journal.pone.0076469</pub-id><pub-id pub-id-type="pmid">24098509</pub-id></element-citation></ref><ref id="B36-diseases-04-00026"><label>36.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Simmons</surname><given-names>G.</given-names></name><name><surname>Gosalia</surname><given-names>D.N.</given-names></name><name><surname>Rennekamp</surname><given-names>A.J.</given-names></name><name><surname>Reeves</surname><given-names>J.D.</given-names></name><name><surname>Diamond</surname><given-names>S.L.</given-names></name><name><surname>Bates</surname><given-names>P.</given-names></name></person-group><article-title>Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2005</year><volume>102</volume><fpage>11876</fpage><lpage>11881</lpage><pub-id pub-id-type="doi">10.1073/pnas.0505577102</pub-id><pub-id pub-id-type="pmid">16081529</pub-id></element-citation></ref><ref id="B37-diseases-04-00026"><label>37.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bertram</surname><given-names>S.</given-names></name><name><surname>Dijkman</surname><given-names>R.</given-names></name><name><surname>Habjan</surname><given-names>M.</given-names></name><name><surname>Heurich</surname><given-names>A.</given-names></name><name><surname>Gierer</surname><given-names>S.</given-names></name><name><surname>Glowacka</surname><given-names>I.</given-names></name><name><surname>Welsch</surname><given-names>K.</given-names></name><name><surname>Winkler</surname><given-names>M.</given-names></name><name><surname>Schneider</surname><given-names>H.</given-names></name><name><surname>Hofmann-Winkler</surname><given-names>H.</given-names></name><etal></etal></person-group><article-title>TMPRSS2 Activates the Human Coronavirus 229E for Cathepsin-Independent Host Cell Entry and Is Expressed in Viral Target Cells in the Respiratory Epithelium</article-title><source>J. Virol.</source><year>2013</year><volume>87</volume><fpage>6150</fpage><lpage>6160</lpage><pub-id pub-id-type="doi">10.1128/JVI.03372-12</pub-id><pub-id pub-id-type="pmid">23536651</pub-id></element-citation></ref><ref id="B38-diseases-04-00026"><label>38.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bertram</surname><given-names>S.</given-names></name><name><surname>Glowacka</surname><given-names>I.</given-names></name><name><surname>Müller</surname><given-names>M.A.</given-names></name><name><surname>Lavender</surname><given-names>H.</given-names></name><name><surname>Gnirss</surname><given-names>K.</given-names></name><name><surname>Nehlmeier</surname><given-names>I.</given-names></name><name><surname>Niemeyer</surname><given-names>D.</given-names></name><name><surname>He</surname><given-names>Y.</given-names></name><name><surname>Simmons</surname><given-names>G.</given-names></name><name><surname>Drosten</surname><given-names>C.</given-names></name><etal></etal></person-group><article-title>Cleavage and Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by Human Airway Trypsin-Like Protease</article-title><source>J. Virol.</source><year>2011</year><volume>85</volume><fpage>13363</fpage><lpage>13372</lpage><pub-id pub-id-type="doi">10.1128/JVI.05300-11</pub-id><pub-id pub-id-type="pmid">21994442</pub-id></element-citation></ref><ref id="B39-diseases-04-00026"><label>39.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Millet</surname><given-names>J.K.</given-names></name><name><surname>Whittaker</surname><given-names>G.R.</given-names></name></person-group><article-title>Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2014</year><volume>111</volume><fpage>15214</fpage><lpage>15219</lpage><pub-id pub-id-type="doi">10.1073/pnas.1407087111</pub-id><pub-id pub-id-type="pmid">25288733</pub-id></element-citation></ref><ref id="B40-diseases-04-00026"><label>40.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>I.C.</given-names></name><name><surname>Bailey</surname><given-names>C.C.</given-names></name><name><surname>Weyer</surname><given-names>J.L.</given-names></name><name><surname>Radoshitzky</surname><given-names>S.R.</given-names></name><name><surname>Becker</surname><given-names>M.M.</given-names></name><name><surname>Chiang</surname><given-names>J.J.</given-names></name><name><surname>Brass</surname><given-names>A.L.</given-names></name><name><surname>Ahmed</surname><given-names>A.A.</given-names></name><name><surname>Chi</surname><given-names>X.</given-names></name><name><surname>Dong</surname><given-names>L.</given-names></name><etal></etal></person-group><article-title>Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus</article-title><source>PLoS Pathog.</source><year>2011</year><volume>7</volume><elocation-id>e1001258</elocation-id><pub-id pub-id-type="doi">10.1371/journal.ppat.1001258</pub-id><pub-id pub-id-type="pmid">21253575</pub-id></element-citation></ref><ref id="B41-diseases-04-00026"><label>41.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>K.</given-names></name><name><surname>Markosyan</surname><given-names>R.M.</given-names></name><name><surname>Zheng</surname><given-names>Y.-M.</given-names></name><name><surname>Golfetto</surname><given-names>O.</given-names></name><name><surname>Bungart</surname><given-names>B.</given-names></name><name><surname>Li</surname><given-names>M.</given-names></name><name><surname>Ding</surname><given-names>S.</given-names></name><name><surname>He</surname><given-names>Y.</given-names></name><name><surname>Liang</surname><given-names>C.</given-names></name><name><surname>Lee</surname><given-names>J.C.</given-names></name><etal></etal></person-group><article-title>IFITM Proteins Restrict Viral Membrane Hemifusion</article-title><source>PLoS Pathog.</source><year>2013</year><volume>9</volume><elocation-id>e1003124</elocation-id><pub-id pub-id-type="doi">10.1371/journal.ppat.1003124</pub-id><pub-id pub-id-type="pmid">23358889</pub-id></element-citation></ref><ref id="B42-diseases-04-00026"><label>42.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Luo</surname><given-names>H.</given-names></name><name><surname>Chen</surname><given-names>Q.</given-names></name><name><surname>Chen</surname><given-names>J.</given-names></name><name><surname>Chen</surname><given-names>K.</given-names></name><name><surname>Shen</surname><given-names>X.</given-names></name><name><surname>Jiang</surname><given-names>H.</given-names></name></person-group><article-title>The nucleocapsid protein of SARS coronavirus has a high binding affinity to the human cellular heterogeneous nuclear ribonucleoprotein A1</article-title><source>FEBS Lett.</source><year>2005</year><volume>579</volume><fpage>2623</fpage><lpage>2628</lpage><pub-id pub-id-type="doi">10.1016/j.febslet.2005.03.080</pub-id><pub-id pub-id-type="pmid">15862300</pub-id></element-citation></ref><ref id="B43-diseases-04-00026"><label>43.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nanda</surname><given-names>S.K.</given-names></name><name><surname>Leibowitz</surname><given-names>J.L.</given-names></name></person-group><article-title>Mitochondrial Aconitase Binds to the 3′ Untranslated Region of the Mouse Hepatitis Virus Genome</article-title><source>J. Virol.</source><year>2001</year><volume>75</volume><fpage>3352</fpage><lpage>3362</lpage><pub-id pub-id-type="doi">10.1128/JVI.75.7.3352-3362.2001</pub-id><pub-id pub-id-type="pmid">11238861</pub-id></element-citation></ref><ref id="B44-diseases-04-00026"><label>44.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wu</surname><given-names>C.-H.</given-names></name><name><surname>Chen</surname><given-names>P.-J.</given-names></name><name><surname>Yeh</surname><given-names>S.-H.</given-names></name></person-group><article-title>Nucleocapsid Phosphorylation and RNA Helicase DDX1 Recruitment Enables Coronavirus Transition from Discontinuous to Continuous Transcription</article-title><source>Cell Host Microb.</source><year>2014</year><volume>16</volume><fpage>462</fpage><lpage>472</lpage><pub-id pub-id-type="doi">10.1016/j.chom.2014.09.009</pub-id><pub-id pub-id-type="pmid">25299332</pub-id></element-citation></ref><ref id="B45-diseases-04-00026"><label>45.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tan</surname><given-names>Y.W.</given-names></name><name><surname>Hong</surname><given-names>W.</given-names></name><name><surname>Liu</surname><given-names>D.X.</given-names></name></person-group><article-title>Binding of the 5′-untranslated region of coronavirus RNA to zinc finger CCHC-type and RNA-binding motif 1 enhances viral replication and transcription</article-title><source>Nucleic Acids Res.</source><year>2012</year><volume>40</volume><fpage>5065</fpage><lpage>5077</lpage><pub-id pub-id-type="doi">10.1093/nar/gks165</pub-id><pub-id pub-id-type="pmid">22362731</pub-id></element-citation></ref><ref id="B46-diseases-04-00026"><label>46.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Neuman</surname><given-names>B.W.</given-names></name><name><surname>Kiss</surname><given-names>G.</given-names></name><name><surname>Kunding</surname><given-names>A.H.</given-names></name><name><surname>Bhella</surname><given-names>D.</given-names></name><name><surname>Baksh</surname><given-names>M.F.</given-names></name><name><surname>Connelly</surname><given-names>S.</given-names></name><name><surname>Droese</surname><given-names>B.</given-names></name><name><surname>Klaus</surname><given-names>J.P.</given-names></name><name><surname>Makino</surname><given-names>S.</given-names></name><name><surname>Sawicki</surname><given-names>S.G.</given-names></name><etal></etal></person-group><article-title>A structural analysis of M protein in coronavirus assembly and morphology</article-title><source>J. Struct. Biol.</source><year>2011</year><volume>174</volume><fpage>11</fpage><lpage>22</lpage><pub-id pub-id-type="doi">10.1016/j.jsb.2010.11.021</pub-id><pub-id pub-id-type="pmid">21130884</pub-id></element-citation></ref><ref id="B47-diseases-04-00026"><label>47.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Luo</surname><given-names>H.</given-names></name><name><surname>Wu</surname><given-names>D.</given-names></name><name><surname>Shen</surname><given-names>C.</given-names></name><name><surname>Chen</surname><given-names>K.</given-names></name><name><surname>Shen</surname><given-names>X.</given-names></name><name><surname>Jiang</surname><given-names>H.</given-names></name></person-group><article-title>Severe acute respiratory syndrome coronavirus membrane protein interacts with nucleocapsid protein mostly through their carboxyl termini by electrostatic attraction</article-title><source>Int. J. Biochem. Cell Biol.</source><year>2006</year><volume>38</volume><fpage>589</fpage><lpage>599</lpage><pub-id pub-id-type="doi">10.1016/j.biocel.2005.10.022</pub-id><pub-id pub-id-type="pmid">16343974</pub-id></element-citation></ref><ref id="B48-diseases-04-00026"><label>48.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wong</surname><given-names>H.H.</given-names></name><name><surname>Kumar</surname><given-names>P.</given-names></name><name><surname>Tay</surname><given-names>F.P.L.</given-names></name><name><surname>Moreau</surname><given-names>D.</given-names></name><name><surname>Liu</surname><given-names>D.X.</given-names></name><name><surname>Bard</surname><given-names>F.</given-names></name></person-group><article-title>Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes</article-title><source>J. Virol.</source><year>2015</year><volume>89</volume><fpage>11116</fpage><lpage>11128</lpage><pub-id pub-id-type="doi">10.1128/JVI.01360-15</pub-id><pub-id pub-id-type="pmid">26311884</pub-id></element-citation></ref><ref id="B49-diseases-04-00026"><label>49.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kerr</surname><given-names>J.F.R.</given-names></name><name><surname>Wyllie</surname><given-names>A.H.</given-names></name><name><surname>Currie</surname><given-names>A.R.</given-names></name></person-group><article-title>Apoptosis: A Basic Biological Phenomenon with Wide-ranging Implications in Tissue Kinetics</article-title><source>Br. J. Cancer</source><year>1972</year><volume>26</volume><fpage>239</fpage><lpage>257</lpage><pub-id pub-id-type="doi">10.1038/bjc.1972.33</pub-id><pub-id pub-id-type="pmid">4561027</pub-id></element-citation></ref><ref id="B50-diseases-04-00026"><label>50.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Boulares</surname><given-names>A.H.</given-names></name><name><surname>Yakovlev</surname><given-names>A.G.</given-names></name><name><surname>Ivanova</surname><given-names>V.</given-names></name><name><surname>Stoica</surname><given-names>B.A.</given-names></name><name><surname>Wang</surname><given-names>G.</given-names></name><name><surname>Iyer</surname><given-names>S.</given-names></name><name><surname>Smulson</surname><given-names>M.</given-names></name></person-group><article-title>Role of Poly(ADP-ribose) Polymerase (PARP) Cleavage in Apoptosis: Caspase 3-resistant parp mutant increases rates of apoptosis in transfected cells</article-title><source>J. Biol. Chem.</source><year>1999</year><volume>274</volume><fpage>22932</fpage><lpage>22940</lpage><pub-id pub-id-type="doi">10.1074/jbc.274.33.22932</pub-id><pub-id pub-id-type="pmid">10438458</pub-id></element-citation></ref><ref id="B51-diseases-04-00026"><label>51.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Segawa</surname><given-names>K.</given-names></name><name><surname>Kurata</surname><given-names>S.</given-names></name><name><surname>Yanagihashi</surname><given-names>Y.</given-names></name><name><surname>Brummelkamp</surname><given-names>T.R.</given-names></name><name><surname>Matsuda</surname><given-names>F.</given-names></name><name><surname>Nagata</surname><given-names>S.</given-names></name></person-group><article-title>Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure</article-title><source>Science</source><year>2014</year><volume>344</volume><fpage>1164</fpage><lpage>1168</lpage><pub-id pub-id-type="doi">10.1126/science.1252809</pub-id><pub-id pub-id-type="pmid">24904167</pub-id></element-citation></ref><ref id="B52-diseases-04-00026"><label>52.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Walczak</surname><given-names>H.</given-names></name><name><surname>Krammer</surname><given-names>P.H.</given-names></name></person-group><article-title>The CD95 (APO-1/Fas) and the TRAIL (APO-2L) Apoptosis Systems</article-title><source>Exp. Cell Res.</source><year>2000</year><volume>256</volume><fpage>58</fpage><lpage>66</lpage><pub-id pub-id-type="doi">10.1006/excr.2000.4840</pub-id><pub-id pub-id-type="pmid">10739652</pub-id></element-citation></ref><ref id="B53-diseases-04-00026"><label>53.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bender</surname><given-names>L.M.</given-names></name><name><surname>Morgan</surname><given-names>M.J.</given-names></name><name><surname>Thomas</surname><given-names>L.R.</given-names></name><name><surname>Liu</surname><given-names>Z.G.</given-names></name><name><surname>Thorburn</surname><given-names>A.</given-names></name></person-group><article-title>The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm</article-title><source>Cell Death Differ.</source><year>2005</year><volume>12</volume><fpage>473</fpage><lpage>481</lpage><pub-id pub-id-type="doi">10.1038/sj.cdd.4401578</pub-id><pub-id pub-id-type="pmid">15761471</pub-id></element-citation></ref><ref id="B54-diseases-04-00026"><label>54.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stennicke</surname><given-names>H.R.</given-names></name><name><surname>Jürgensmeier</surname><given-names>J.M.</given-names></name><name><surname>Shin</surname><given-names>H.</given-names></name><name><surname>Deveraux</surname><given-names>Q.</given-names></name><name><surname>Wolf</surname><given-names>B.B.</given-names></name><name><surname>Yang</surname><given-names>X.</given-names></name><name><surname>Zhou</surname><given-names>Q.</given-names></name><name><surname>Ellerby</surname><given-names>H.M.</given-names></name><name><surname>Ellerby</surname><given-names>L.M.</given-names></name><name><surname>Bredesen</surname><given-names>D.</given-names></name><etal></etal></person-group><article-title>Pro-caspase-3 Is a Major Physiologic Target of Caspase-8</article-title><source>J. Biol. Chem.</source><year>1998</year><volume>273</volume><fpage>27084</fpage><lpage>27090</lpage><pub-id pub-id-type="doi">10.1074/jbc.273.42.27084</pub-id><pub-id pub-id-type="pmid">9765224</pub-id></element-citation></ref><ref id="B55-diseases-04-00026"><label>55.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Taylor</surname><given-names>R.C.</given-names></name><name><surname>Cullen</surname><given-names>S.P.</given-names></name><name><surname>Martin</surname><given-names>S.J.</given-names></name></person-group><article-title>Apoptosis: Controlled demolition at the cellular level</article-title><source>Nat. Rev. Mol. Cell Biol.</source><year>2008</year><volume>9</volume><fpage>231</fpage><lpage>241</lpage><pub-id pub-id-type="doi">10.1038/nrm2312</pub-id><pub-id pub-id-type="pmid">18073771</pub-id></element-citation></ref><ref id="B56-diseases-04-00026"><label>56.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sebbagh</surname><given-names>M.</given-names></name><name><surname>Renvoize</surname><given-names>C.</given-names></name><name><surname>Hamelin</surname><given-names>J.</given-names></name><name><surname>Riche</surname><given-names>N.</given-names></name><name><surname>Bertoglio</surname><given-names>J.</given-names></name><name><surname>Breard</surname><given-names>J.</given-names></name></person-group><article-title>Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing</article-title><source>Nat. Cell Biol.</source><year>2001</year><volume>3</volume><fpage>346</fpage><lpage>352</lpage><pub-id pub-id-type="doi">10.1038/35070019</pub-id><pub-id pub-id-type="pmid">11283607</pub-id></element-citation></ref><ref id="B57-diseases-04-00026"><label>57.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>H.</given-names></name><name><surname>Zhu</surname><given-names>H.</given-names></name><name><surname>Xu</surname><given-names>C.-J.</given-names></name><name><surname>Yuan</surname><given-names>J.</given-names></name></person-group><article-title>Cleavage of BID by Caspase 8 Mediates the Mitochondrial Damage in the Fas Pathway of Apoptosis</article-title><source>Cell</source><year>1998</year><volume>94</volume><fpage>491</fpage><lpage>501</lpage><pub-id pub-id-type="doi">10.1016/S0092-8674(00)81590-1</pub-id><pub-id pub-id-type="pmid">9727492</pub-id></element-citation></ref><ref id="B58-diseases-04-00026"><label>58.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Benedict</surname><given-names>C.A.</given-names></name><name><surname>Norris</surname><given-names>P.S.</given-names></name><name><surname>Ware</surname><given-names>C.F.</given-names></name></person-group><article-title>To kill or be killed: Viral evasion of apoptosis</article-title><source>Nat. Immunol.</source><year>2002</year><volume>3</volume><fpage>1013</fpage><lpage>1018</lpage><pub-id pub-id-type="doi">10.1038/ni1102-1013</pub-id><pub-id pub-id-type="pmid">12407409</pub-id></element-citation></ref><ref id="B59-diseases-04-00026"><label>59.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kvansakul</surname><given-names>M.</given-names></name><name><surname>Hinds</surname><given-names>M.G.</given-names></name></person-group><article-title>Structural biology of the Bcl-2 family and its mimicry by viral proteins</article-title><source>Cell Death Dis.</source><year>2013</year><volume>4</volume><fpage>e909</fpage><pub-id pub-id-type="doi">10.1038/cddis.2013.436</pub-id><pub-id pub-id-type="pmid">24201808</pub-id></element-citation></ref><ref id="B60-diseases-04-00026"><label>60.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pearce</surname><given-names>A.F.</given-names></name><name><surname>Lyles</surname><given-names>D.S.</given-names></name></person-group><article-title>Vesicular Stomatitis Virus Induces Apoptosis Primarily through Bak Rather than Bax by Inactivating Mcl-1 and Bcl-XL</article-title><source>J. Virol.</source><year>2009</year><volume>83</volume><fpage>9102</fpage><lpage>9112</lpage><pub-id pub-id-type="doi">10.1128/JVI.00436-09</pub-id><pub-id pub-id-type="pmid">19587033</pub-id></element-citation></ref><ref id="B61-diseases-04-00026"><label>61.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aillet</surname><given-names>F.</given-names></name><name><surname>Masutani</surname><given-names>H.</given-names></name><name><surname>Elbim</surname><given-names>C.</given-names></name><name><surname>Raoul</surname><given-names>H.</given-names></name><name><surname>Chêne</surname><given-names>L.</given-names></name><name><surname>Nugeyre</surname><given-names>M.T.</given-names></name><name><surname>Paya</surname><given-names>C.</given-names></name><name><surname>Barré-Sinoussi</surname><given-names>F.</given-names></name><name><surname>Gougerot-Pocidalo</surname><given-names>M.A.</given-names></name><name><surname>Israël</surname><given-names>N.</given-names></name></person-group><article-title>Human immunodeficiency virus induces a dual regulation of Bcl-2, resulting in persistent infection of CD4(+) T- or monocytic cell lines</article-title><source>J. Virol.</source><year>1998</year><volume>72</volume><fpage>9698</fpage><lpage>9705</lpage><pub-id pub-id-type="pmid">9811703</pub-id></element-citation></ref><ref id="B62-diseases-04-00026"><label>62.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tamura</surname><given-names>R.</given-names></name><name><surname>Kanda</surname><given-names>T.</given-names></name><name><surname>Imazeki</surname><given-names>F.</given-names></name><name><surname>Wu</surname><given-names>S.</given-names></name><name><surname>Nakamoto</surname><given-names>S.</given-names></name><name><surname>Tanaka</surname><given-names>T.</given-names></name><name><surname>Arai</surname><given-names>M.</given-names></name><name><surname>Fujiwara</surname><given-names>K.</given-names></name><name><surname>Saito</surname><given-names>K.</given-names></name><name><surname>Roger</surname><given-names>T.</given-names></name><etal></etal></person-group><article-title>Hepatitis C Virus Nonstructural 5A Protein Inhibits Lipopolysaccharide-Mediated Apoptosis of Hepatocytes by Decreasing Expression of Toll-Like Receptor 4</article-title><source>J. Infect. Dis.</source><year>2011</year><volume>204</volume><fpage>793</fpage><lpage>801</lpage><pub-id pub-id-type="doi">10.1093/infdis/jir381</pub-id><pub-id pub-id-type="pmid">21844306</pub-id></element-citation></ref><ref id="B63-diseases-04-00026"><label>63.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aweya</surname><given-names>J.J.</given-names></name><name><surname>Sze</surname><given-names>C.W.</given-names></name><name><surname>Bayega</surname><given-names>A.</given-names></name><name><surname>Mohd-Ismail</surname><given-names>N.K.</given-names></name><name><surname>Deng</surname><given-names>L.</given-names></name><name><surname>Hotta</surname><given-names>H.</given-names></name><name><surname>Tan</surname><given-names>Y.J.</given-names></name></person-group><article-title>NS5B induces up-regulation of the BH3-only protein, BIK, essential for the hepatitis C virus RNA replication and viral release</article-title><source>Virology</source><year>2015</year><volume>474</volume><fpage>41</fpage><lpage>51</lpage><pub-id pub-id-type="doi">10.1016/j.virol.2014.10.027</pub-id><pub-id pub-id-type="pmid">25463603</pub-id></element-citation></ref><ref id="B64-diseases-04-00026"><label>64.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nakamura-Lopez</surname><given-names>Y.</given-names></name><name><surname>Villegas-Sepúlveda</surname><given-names>N.</given-names></name><name><surname>Gómez</surname><given-names>B.</given-names></name></person-group><article-title>RSV P-protein impairs extrinsic apoptosis pathway in a macrophage-like cell line persistently infected with respiratory syncytial virus</article-title><source>Virus Res.</source><year>2015</year><volume>204</volume><fpage>82</fpage><lpage>87</lpage><pub-id pub-id-type="doi">10.1016/j.virusres.2015.04.018</pub-id><pub-id pub-id-type="pmid">25937519</pub-id></element-citation></ref><ref id="B65-diseases-04-00026"><label>65.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mocarski</surname><given-names>E.S.</given-names></name><name><surname>Upton</surname><given-names>J.W.</given-names></name><name><surname>Kaiser</surname><given-names>W.J.</given-names></name></person-group><article-title>Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways</article-title><source>Nat. Rev. Immunol.</source><year>2012</year><volume>12</volume><fpage>79</fpage><lpage>88</lpage><pub-id pub-id-type="doi">10.1038/nri3131</pub-id><pub-id pub-id-type="pmid">22193709</pub-id></element-citation></ref><ref id="B66-diseases-04-00026"><label>66.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amara</surname><given-names>A.</given-names></name><name><surname>Mercer</surname><given-names>J.</given-names></name></person-group><article-title>Viral apoptotic mimicry</article-title><source>Nat. Rev. Microbiol.</source><year>2015</year><volume>13</volume><fpage>461</fpage><lpage>469</lpage><pub-id pub-id-type="doi">10.1038/nrmicro3469</pub-id><pub-id pub-id-type="pmid">26052667</pub-id></element-citation></ref><ref id="B67-diseases-04-00026"><label>67.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Collins</surname><given-names>A.R.</given-names></name></person-group><article-title>Induction of Apoptosis in MRC-5, Diploid Human Fetal Lung Cells after Infection with Human Coronavirus OC43</article-title><source>The Nidoviruses: Coronaviruses and Arteriviruses</source><person-group person-group-type="editor"><name><surname>Lavi</surname><given-names>E.</given-names></name><name><surname>Weiss</surname><given-names>S.R.</given-names></name><name><surname>Hingley</surname><given-names>S.T.</given-names></name></person-group><publisher-name>Springer US</publisher-name><publisher-loc>Boston, MA, USA</publisher-loc><year>2001</year><fpage>677</fpage><lpage>682</lpage></element-citation></ref><ref id="B68-diseases-04-00026"><label>68.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pyrc</surname><given-names>K.</given-names></name><name><surname>Berkhout</surname><given-names>B.</given-names></name><name><surname>van der Hoek</surname><given-names>L.</given-names></name></person-group><article-title>The Novel Human Coronaviruses NL63 and HKU1</article-title><source>J. Virol.</source><year>2007</year><volume>81</volume><fpage>3051</fpage><lpage>3057</lpage><pub-id pub-id-type="doi">10.1128/JVI.01466-06</pub-id><pub-id pub-id-type="pmid">17079323</pub-id></element-citation></ref><ref id="B69-diseases-04-00026"><label>69.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gu</surname><given-names>J.</given-names></name><name><surname>Korteweg</surname><given-names>C.</given-names></name></person-group><article-title>Pathology and Pathogenesis of Severe Acute Respiratory Syndrome</article-title><source>Am. J. Pathol.</source><year>2007</year><volume>170</volume><fpage>1136</fpage><lpage>1147</lpage><pub-id pub-id-type="doi">10.2353/ajpath.2007.061088</pub-id><pub-id pub-id-type="pmid">17392154</pub-id></element-citation></ref><ref id="B70-diseases-04-00026"><label>70.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tao</surname><given-names>X.</given-names></name><name><surname>Hill</surname><given-names>T.E.</given-names></name><name><surname>Morimoto</surname><given-names>C.</given-names></name><name><surname>Peters</surname><given-names>C.J.</given-names></name><name><surname>Ksiazek</surname><given-names>T.G.</given-names></name><name><surname>Tseng</surname><given-names>C.-T.K.</given-names></name></person-group><article-title>Bilateral Entry and Release of Middle East Respiratory Syndrome Coronavirus Induces Profound Apoptosis of Human Bronchial Epithelial Cells</article-title><source>J. Virol.</source><year>2013</year><volume>87</volume><fpage>9953</fpage><lpage>9958</lpage><pub-id pub-id-type="doi">10.1128/JVI.01562-13</pub-id><pub-id pub-id-type="pmid">23824802</pub-id></element-citation></ref><ref id="B71-diseases-04-00026"><label>71.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yeung</surname><given-names>M.-L.</given-names></name><name><surname>Yao</surname><given-names>Y.</given-names></name><name><surname>Jia</surname><given-names>L.</given-names></name><name><surname>Chan</surname><given-names>J.F.W.</given-names></name><name><surname>Chan</surname><given-names>K.-H.</given-names></name><name><surname>Cheung</surname><given-names>K.-F.</given-names></name><name><surname>Chen</surname><given-names>H.</given-names></name><name><surname>Poon</surname><given-names>V.K.M.</given-names></name><name><surname>Tsang</surname><given-names>A.K.L.</given-names></name><name><surname>To</surname><given-names>K.K.W.</given-names></name><etal></etal></person-group><article-title>MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2</article-title><source>Nat. Microbiol.</source><year>2016</year><volume>1</volume><fpage>16004</fpage><pub-id pub-id-type="doi">10.1038/nmicrobiol.2016.4</pub-id><pub-id pub-id-type="pmid">27572168</pub-id></element-citation></ref><ref id="B72-diseases-04-00026"><label>72.</label><element-citation publication-type="confproc"><person-group person-group-type="author"><name><surname>Desforges</surname><given-names>M.</given-names></name><name><surname>Coupanec</surname><given-names>A.</given-names></name><name><surname>Brison</surname><given-names>É.</given-names></name><name><surname>Meessen-Pinard</surname><given-names>M.</given-names></name><name><surname>Talbot</surname><given-names>P.J.</given-names></name></person-group><article-title>Neuroinvasive and Neurotropic Human Respiratory Coronaviruses: Potential Neurovirulent Agents in Humans</article-title><source>Proceedings of the Infectious Diseases and Nanomedicine I: First International Conference (ICIDN-2012)</source><conf-loc>Kathmandu, Nepal</conf-loc><conf-date>15–18 December 2012</conf-date><person-group person-group-type="editor"><name><surname>Adhikari</surname><given-names>R.</given-names></name><name><surname>Thapa</surname><given-names>S.</given-names></name></person-group><publisher-name>Springer</publisher-name><publisher-loc>New Delhi, India</publisher-loc><year>2014</year><fpage>75</fpage><lpage>96</lpage></element-citation></ref><ref id="B73-diseases-04-00026"><label>73.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Desforges</surname><given-names>M.</given-names></name><name><surname>Le Coupanec</surname><given-names>A.</given-names></name><name><surname>Stodola</surname><given-names>J.K.</given-names></name><name><surname>Meessen-Pinard</surname><given-names>M.</given-names></name><name><surname>Talbot</surname><given-names>P.J.</given-names></name></person-group><article-title>Human coronaviruses: Viral and cellular factors involved in neuroinvasiveness and neuropathogenesis</article-title><source>Virus Res.</source><year>2014</year><volume>194</volume><fpage>145</fpage><lpage>158</lpage><pub-id pub-id-type="doi">10.1016/j.virusres.2014.09.011</pub-id><pub-id pub-id-type="pmid">25281913</pub-id></element-citation></ref><ref id="B74-diseases-04-00026"><label>74.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Favreau</surname><given-names>D.J.</given-names></name><name><surname>Meessen-Pinard</surname><given-names>M.</given-names></name><name><surname>Desforges</surname><given-names>M.</given-names></name><name><surname>Talbot</surname><given-names>P.J.</given-names></name></person-group><article-title>Human Coronavirus-Induced Neuronal Programmed Cell Death Is Cyclophilin D Dependent and Potentially Caspase Dispensable</article-title><source>J. Virol.</source><year>2012</year><volume>86</volume><fpage>81</fpage><lpage>93</lpage><pub-id pub-id-type="doi">10.1128/JVI.06062-11</pub-id><pub-id pub-id-type="pmid">22013052</pub-id></element-citation></ref><ref id="B75-diseases-04-00026"><label>75.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Krähling</surname><given-names>V.</given-names></name><name><surname>Stein</surname><given-names>D.A.</given-names></name><name><surname>Spiegel</surname><given-names>M.</given-names></name><name><surname>Weber</surname><given-names>F.</given-names></name><name><surname>Mühlberger</surname><given-names>E.</given-names></name></person-group><article-title>Severe Acute Respiratory Syndrome Coronavirus Triggers Apoptosis via Protein Kinase R but Is Resistant to Its Antiviral Activity</article-title><source>J. Virol.</source><year>2009</year><volume>83</volume><fpage>2298</fpage><lpage>2309</lpage><pub-id pub-id-type="doi">10.1128/JVI.01245-08</pub-id><pub-id pub-id-type="pmid">19109397</pub-id></element-citation></ref><ref id="B76-diseases-04-00026"><label>76.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Collins</surname><given-names>A.R.</given-names></name></person-group><article-title>In Vitro Detection of Apoptosis in Monocytes/Macrophages Infected with Human Coronavirus</article-title><source>Clin. Diagn. Lab. Immunol.</source><year>2002</year><volume>9</volume><fpage>1392</fpage><lpage>1395</lpage><pub-id pub-id-type="doi">10.1128/CDLI.9.6.1392-1395.2002</pub-id><pub-id pub-id-type="pmid">12414783</pub-id></element-citation></ref><ref id="B77-diseases-04-00026"><label>77.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>Y.</given-names></name><name><surname>Xiong</surname><given-names>Z.</given-names></name><name><surname>Zhang</surname><given-names>S.</given-names></name><name><surname>Yan</surname><given-names>Y.</given-names></name><name><surname>Nguyen</surname><given-names>J.</given-names></name><name><surname>Ng</surname><given-names>B.</given-names></name><name><surname>Lu</surname><given-names>H.</given-names></name><name><surname>Brendese</surname><given-names>J.</given-names></name><name><surname>Yang</surname><given-names>F.</given-names></name><name><surname>Wang</surname><given-names>H.</given-names></name><etal></etal></person-group><article-title>Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors</article-title><source>Biochem. J.</source><year>2005</year><volume>392</volume><fpage>135</fpage><lpage>143</lpage><pub-id pub-id-type="doi">10.1042/BJ20050698</pub-id><pub-id pub-id-type="pmid">16048439</pub-id></element-citation></ref><ref id="B78-diseases-04-00026"><label>78.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ying</surname><given-names>T.</given-names></name><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Dimitrov</surname><given-names>D.S.</given-names></name></person-group><article-title>Discovery of T-Cell Infection and Apoptosis by Middle East Respiratory Syndrome Coronavirus</article-title><source>J. Infect. Dis.</source><year>2015</year><pub-id pub-id-type="doi">10.1093/infdis/jiv381</pub-id><pub-id pub-id-type="pmid">26203059</pub-id></element-citation></ref><ref id="B79-diseases-04-00026"><label>79.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chu</surname><given-names>H.</given-names></name><name><surname>Zhou</surname><given-names>J.</given-names></name><name><surname>Wong</surname><given-names>B.H.-Y.</given-names></name><name><surname>Li</surname><given-names>C.</given-names></name><name><surname>Chan</surname><given-names>J.F.-W.</given-names></name><name><surname>Cheng</surname><given-names>Z.-S.</given-names></name><name><surname>Yang</surname><given-names>D.</given-names></name><name><surname>Wang</surname><given-names>D.</given-names></name><name><surname>Lee</surname><given-names>A.C.</given-names></name><name><surname>Li</surname><given-names>C.</given-names></name><etal></etal></person-group><article-title>Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways</article-title><source>J. Infect. Dis.</source><year>2016</year><volume>213</volume><fpage>904</fpage><lpage>914</lpage><pub-id pub-id-type="doi">10.1093/infdis/jiv380</pub-id><pub-id pub-id-type="pmid">26203058</pub-id></element-citation></ref><ref id="B80-diseases-04-00026"><label>80.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mesel-Lemoine</surname><given-names>M.</given-names></name><name><surname>Millet</surname><given-names>J.</given-names></name><name><surname>Vidalain</surname><given-names>P.-O.</given-names></name><name><surname>Law</surname><given-names>H.</given-names></name><name><surname>Vabret</surname><given-names>A.</given-names></name><name><surname>Lorin</surname><given-names>V.</given-names></name><name><surname>Escriou</surname><given-names>N.</given-names></name><name><surname>Albert</surname><given-names>M.L.</given-names></name><name><surname>Nal</surname><given-names>B.</given-names></name><name><surname>Tangy</surname><given-names>F.</given-names></name></person-group><article-title>A Human Coronavirus Responsible for the Common Cold Massively Kills Dendritic Cells but Not Monocytes</article-title><source>J. Virol.</source><year>2012</year><volume>86</volume><fpage>7577</fpage><lpage>7587</lpage><pub-id pub-id-type="doi">10.1128/JVI.00269-12</pub-id><pub-id pub-id-type="pmid">22553325</pub-id></element-citation></ref><ref id="B81-diseases-04-00026"><label>81.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Spiegel</surname><given-names>M.</given-names></name><name><surname>Schneider</surname><given-names>K.</given-names></name><name><surname>Weber</surname><given-names>F.</given-names></name><name><surname>Weidmann</surname><given-names>M.</given-names></name><name><surname>Hufert</surname><given-names>F.</given-names></name></person-group><article-title>Interaction of severe acute respiratory syndrome-associated coronavirus with dendritic cells</article-title><source>J. Gen. Virol.</source><year>2006</year><volume>87</volume><fpage>1953</fpage><lpage>1960</lpage><pub-id pub-id-type="doi">10.1099/vir.0.81624-0</pub-id><pub-id pub-id-type="pmid">16760397</pub-id></element-citation></ref><ref id="B82-diseases-04-00026"><label>82.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bordi</surname><given-names>L.</given-names></name><name><surname>Castilletti</surname><given-names>C.</given-names></name><name><surname>Falasca</surname><given-names>L.</given-names></name><name><surname>Ciccosanti</surname><given-names>F.</given-names></name><name><surname>Calcaterra</surname><given-names>S.</given-names></name><name><surname>Rozera</surname><given-names>G.</given-names></name><name><surname>Di Caro</surname><given-names>A.</given-names></name><name><surname>Zaniratti</surname><given-names>S.</given-names></name><name><surname>Rinaldi</surname><given-names>A.</given-names></name><name><surname>Ippolito</surname><given-names>G.</given-names></name><etal></etal></person-group><article-title>Bcl-2 inhibits the caspase-dependent apoptosis induced by SARS-CoV without affecting virus replication kinetics</article-title><source>Arch. Virol.</source><year>2005</year><volume>151</volume><fpage>369</fpage><lpage>377</lpage><pub-id pub-id-type="doi">10.1007/s00705-005-0632-8</pub-id><pub-id pub-id-type="pmid">16155806</pub-id></element-citation></ref><ref id="B83-diseases-04-00026"><label>83.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ren</surname><given-names>L.</given-names></name><name><surname>Yang</surname><given-names>R.</given-names></name><name><surname>Guo</surname><given-names>L.</given-names></name><name><surname>Qu</surname><given-names>J.</given-names></name><name><surname>Wang</surname><given-names>J.</given-names></name><name><surname>Hung</surname><given-names>T.</given-names></name></person-group><article-title>Apoptosis Induced by the SARS-Associated Coronavirus in Vero Cells Is Replication-Dependent and Involves Caspase</article-title><source>DNA Cell Biol.</source><year>2005</year><volume>24</volume><fpage>496</fpage><lpage>502</lpage><pub-id pub-id-type="doi">10.1089/dna.2005.24.496</pub-id><pub-id pub-id-type="pmid">16101347</pub-id></element-citation></ref><ref id="B84-diseases-04-00026"><label>84.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tang</surname><given-names>B.S.F.</given-names></name><name><surname>Chan</surname><given-names>K.-h.</given-names></name><name><surname>Cheng</surname><given-names>V.C.C.</given-names></name><name><surname>Woo</surname><given-names>P.C.Y.</given-names></name><name><surname>Lau</surname><given-names>S.K.P.</given-names></name><name><surname>Lam</surname><given-names>C.C.K.</given-names></name><name><surname>Chan</surname><given-names>T.L.</given-names></name><name><surname>Wu</surname><given-names>A.K.</given-names></name><name><surname>Hung</surname><given-names>I.F.</given-names></name><name><surname>Leung</surname><given-names>S.Y.</given-names></name><etal></etal></person-group><article-title>Comparative Host Gene Transcription by Microarray Analysis Early after Infection of the Huh7 Cell Line by Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus 229E</article-title><source>J. Virol.</source><year>2005</year><volume>79</volume><fpage>6180</fpage><lpage>6193</lpage><pub-id pub-id-type="doi">10.1128/JVI.79.10.6180-6193.2005</pub-id><pub-id pub-id-type="pmid">15858003</pub-id></element-citation></ref><ref id="B85-diseases-04-00026"><label>85.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chow</surname><given-names>K.Y.C.</given-names></name><name><surname>Yeung</surname><given-names>Y.S.</given-names></name><name><surname>Hon</surname><given-names>C.C.</given-names></name><name><surname>Zeng</surname><given-names>F.</given-names></name><name><surname>Law</surname><given-names>K.M.</given-names></name><name><surname>Leung</surname><given-names>F.C.C.</given-names></name></person-group><article-title>Adenovirus-mediated expression of the C-terminal domain of SARS-CoV spike protein is sufficient to induce apoptosis in Vero E6 cells</article-title><source>FEBS Lett.</source><year>2005</year><volume>579</volume><fpage>6699</fpage><lpage>6704</lpage><pub-id pub-id-type="doi">10.1016/j.febslet.2005.10.065</pub-id><pub-id pub-id-type="pmid">16310778</pub-id></element-citation></ref><ref id="B86-diseases-04-00026"><label>86.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Surjit</surname><given-names>M.</given-names></name><name><surname>Liu</surname><given-names>B.</given-names></name><name><surname>Jameel</surname><given-names>S.</given-names></name><name><surname>Chow</surname><given-names>V.T.K.</given-names></name><name><surname>Lal</surname><given-names>S.K.</given-names></name></person-group><article-title>The SARS coronavirus nucleocapsid protein induces actin reorganization and apoptosis in COS-1 cells in the absence of growth factors</article-title><source>Biochem. J.</source><year>2004</year><volume>383</volume><fpage>13</fpage><lpage>18</lpage><pub-id pub-id-type="doi">10.1042/BJ20040984</pub-id><pub-id pub-id-type="pmid">15294014</pub-id></element-citation></ref><ref id="B87-diseases-04-00026"><label>87.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tan</surname><given-names>Y.-J.</given-names></name><name><surname>Fielding</surname><given-names>B.C.</given-names></name><name><surname>Goh</surname><given-names>P.-Y.</given-names></name><name><surname>Shen</surname><given-names>S.</given-names></name><name><surname>Tan</surname><given-names>T.H.P.</given-names></name><name><surname>Lim</surname><given-names>S.G.</given-names></name><name><surname>Hong</surname><given-names>W.</given-names></name></person-group><article-title>Overexpression of 7a, a Protein Specifically Encoded by the Severe Acute Respiratory Syndrome Coronavirus, Induces Apoptosis via a Caspase-Dependent Pathway</article-title><source>J. Virol.</source><year>2004</year><volume>78</volume><fpage>14043</fpage><lpage>14047</lpage><pub-id pub-id-type="doi">10.1128/JVI.78.24.14043-14047.2004</pub-id><pub-id pub-id-type="pmid">15564512</pub-id></element-citation></ref><ref id="B88-diseases-04-00026"><label>88.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ye</surname><given-names>Z.</given-names></name><name><surname>Wong</surname><given-names>C.K.</given-names></name><name><surname>Li</surname><given-names>P.</given-names></name><name><surname>Xie</surname><given-names>Y.</given-names></name></person-group><article-title>A SARS-CoV protein, ORF-6, induces caspase-3 mediated, ER stress and JNK-dependent apoptosis</article-title><source>Biochim. Biophys. Acta</source><year>2008</year><volume>1780</volume><fpage>1383</fpage><lpage>1387</lpage><pub-id pub-id-type="doi">10.1016/j.bbagen.2008.07.009</pub-id><pub-id pub-id-type="pmid">18708124</pub-id></element-citation></ref><ref id="B89-diseases-04-00026"><label>89.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sharma</surname><given-names>K.</given-names></name><name><surname>Åkerström</surname><given-names>S.</given-names></name><name><surname>Sharma</surname><given-names>A.K.</given-names></name><name><surname>Chow</surname><given-names>V.T.K.</given-names></name><name><surname>Teow</surname><given-names>S.</given-names></name><name><surname>Abrenica</surname><given-names>B.</given-names></name><name><surname>Booth</surname><given-names>S.A.</given-names></name><name><surname>Booth</surname><given-names>T.F.</given-names></name><name><surname>Mirazimi</surname><given-names>A.</given-names></name><name><surname>Lal</surname><given-names>S.K.</given-names></name></person-group><article-title>SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the Nucleus</article-title><source>PLoS ONE</source><year>2011</year><volume>6</volume><elocation-id>e19436</elocation-id><pub-id pub-id-type="doi">10.1371/journal.pone.0019436</pub-id><pub-id pub-id-type="pmid">21637748</pub-id></element-citation></ref><ref id="B90-diseases-04-00026"><label>90.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tsoi</surname><given-names>H.</given-names></name><name><surname>Li</surname><given-names>L.</given-names></name><name><surname>Chen</surname><given-names>Zhefan S.</given-names></name><name><surname>Lau</surname><given-names>K.-F.</given-names></name><name><surname>Tsui</surname><given-names>S.K.W.</given-names></name><name><surname>Chan</surname><given-names>H.Y.E.</given-names></name></person-group><article-title>The SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1-PKB/Akt signalling</article-title><source>Biochem. J.</source><year>2014</year><volume>464</volume><fpage>439</fpage><lpage>447</lpage><pub-id pub-id-type="doi">10.1042/BJ20131461</pub-id><pub-id pub-id-type="pmid">25271362</pub-id></element-citation></ref><ref id="B91-diseases-04-00026"><label>91.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>De Diego</surname><given-names>M.L.</given-names></name><name><surname>Nieto-Torres</surname><given-names>J.L.</given-names></name><name><surname>JimÈnez-GuardeÒo</surname><given-names>J.M.</given-names></name><name><surname>Regla-Nava</surname><given-names>J.A.</given-names></name><name><surname>Álvarez</surname><given-names>E.</given-names></name><name><surname>Oliveros</surname><given-names>J.C.</given-names></name><name><surname>Zhao</surname><given-names>J.</given-names></name><name><surname>Fett</surname><given-names>C.</given-names></name><name><surname>Perlman</surname><given-names>S.</given-names></name><name><surname>Enjuanes</surname><given-names>L.</given-names></name></person-group><article-title>Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Regulates Cell Stress Response and Apoptosis</article-title><source>PLoS Pathog.</source><year>2011</year><volume>7</volume><elocation-id>e1002315</elocation-id><pub-id pub-id-type="pmid">22028656</pub-id></element-citation></ref><ref id="B92-diseases-04-00026"><label>92.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tan</surname><given-names>Y.-X.</given-names></name><name><surname>Tan</surname><given-names>T.H.P.</given-names></name><name><surname>Lee</surname><given-names>M.J.R.</given-names></name><name><surname>Tham</surname><given-names>P.-Y.</given-names></name><name><surname>Gunalan</surname><given-names>V.</given-names></name><name><surname>Druce</surname><given-names>J.</given-names></name><name><surname>Birch</surname><given-names>C.</given-names></name><name><surname>Catton</surname><given-names>M.</given-names></name><name><surname>Fu</surname><given-names>N.Y.</given-names></name><name><surname>Yu</surname><given-names>V.C.</given-names></name><etal></etal></person-group><article-title>Induction of Apoptosis by the Severe Acute Respiratory Syndrome Coronavirus 7a Protein Is Dependent on Its Interaction with the Bcl-X(L) Protein</article-title><source>J. Virol.</source><year>2007</year><volume>81</volume><fpage>6346</fpage><lpage>6355</lpage><pub-id pub-id-type="doi">10.1128/JVI.00090-07</pub-id><pub-id pub-id-type="pmid">17428862</pub-id></element-citation></ref><ref id="B93-diseases-04-00026"><label>93.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Favreau</surname><given-names>D.J.</given-names></name><name><surname>Desforges</surname><given-names>M.</given-names></name><name><surname>St-Jean</surname><given-names>J.R.</given-names></name><name><surname>Talbot</surname><given-names>P.J.</given-names></name></person-group><article-title>A human coronavirus OC43 variant harboring persistence-associated mutations in the S glycoprotein differentially induces the unfolded protein response in human neurons as compared to wild-type virus</article-title><source>Virology</source><year>2009</year><volume>395</volume><fpage>255</fpage><lpage>267</lpage><pub-id pub-id-type="doi">10.1016/j.virol.2009.09.026</pub-id><pub-id pub-id-type="pmid">19846189</pub-id></element-citation></ref><ref id="B94-diseases-04-00026"><label>94.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Diemer</surname><given-names>C.</given-names></name><name><surname>Schneider</surname><given-names>M.</given-names></name><name><surname>Seebach</surname><given-names>J.</given-names></name><name><surname>Quaas</surname><given-names>J.</given-names></name><name><surname>Frösner</surname><given-names>G.</given-names></name><name><surname>Schätzl</surname><given-names>H.M.</given-names></name><name><surname>Gilch</surname><given-names>S.</given-names></name></person-group><article-title>Cell Type-Specific Cleavage of Nucleocapsid Protein by Effector Caspases during SARS Coronavirus Infection</article-title><source>J. Mol. Biol.</source><year>2008</year><volume>376</volume><fpage>23</fpage><lpage>34</lpage><pub-id pub-id-type="doi">10.1016/j.jmb.2007.11.081</pub-id><pub-id pub-id-type="pmid">18155731</pub-id></element-citation></ref><ref id="B95-diseases-04-00026"><label>95.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alcami</surname><given-names>A.</given-names></name><name><surname>Koszinowski</surname><given-names>U.H.</given-names></name></person-group><article-title>Viral mechanisms of immune evasion</article-title><source>Immunol. Today</source><year>2000</year><volume>21</volume><fpage>447</fpage><lpage>455</lpage><pub-id pub-id-type="doi">10.1016/S0167-5699(00)01699-6</pub-id><pub-id pub-id-type="pmid">10953097</pub-id></element-citation></ref><ref id="B96-diseases-04-00026"><label>96.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bowie</surname><given-names>A.G.</given-names></name><name><surname>Unterholzner</surname><given-names>L.</given-names></name></person-group><article-title>Viral evasion and subversion of pattern-recognition receptor signalling</article-title><source>Nat. Rev. Immunol.</source><year>2008</year><volume>8</volume><fpage>911</fpage><lpage>922</lpage><pub-id pub-id-type="doi">10.1038/nri2436</pub-id><pub-id pub-id-type="pmid">18989317</pub-id></element-citation></ref><ref id="B97-diseases-04-00026"><label>97.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kawai</surname><given-names>T.</given-names></name><name><surname>Akira</surname><given-names>S.</given-names></name></person-group><article-title>Toll-like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immunity</article-title><source>Immunity</source><year>2011</year><volume>34</volume><fpage>637</fpage><lpage>650</lpage><pub-id pub-id-type="doi">10.1016/j.immuni.2011.05.006</pub-id><pub-id pub-id-type="pmid">21616434</pub-id></element-citation></ref><ref id="B98-diseases-04-00026"><label>98.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jensen</surname><given-names>S.</given-names></name><name><surname>Thomsen</surname><given-names>A.R.</given-names></name></person-group><article-title>Sensing of RNA Viruses: A Review of Innate Immune Receptors Involved in Recognizing RNA virus Invasion</article-title><source>J. Virol.</source><year>2012</year><volume>86</volume><fpage>2900</fpage><lpage>2910</lpage><pub-id pub-id-type="doi">10.1128/JVI.05738-11</pub-id><pub-id pub-id-type="pmid">22258243</pub-id></element-citation></ref><ref id="B99-diseases-04-00026"><label>99.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>S.M.Y.</given-names></name><name><surname>Kok</surname><given-names>K.-H.</given-names></name><name><surname>Jaume</surname><given-names>M.</given-names></name><name><surname>Cheung</surname><given-names>T.K.W.</given-names></name><name><surname>Yip</surname><given-names>T.-F.</given-names></name><name><surname>Lai</surname><given-names>J.C.C.</given-names></name><name><surname>Guan</surname><given-names>Y.</given-names></name><name><surname>Webster</surname><given-names>R.G.</given-names></name><name><surname>Jin</surname><given-names>D.Y.</given-names></name><name><surname>Peiris</surname><given-names>J.S.</given-names></name></person-group><article-title>Toll-like receptor 10 is involved in induction of innate immune responses to influenza virus infection</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2014</year><volume>111</volume><fpage>3793</fpage><lpage>3798</lpage><pub-id pub-id-type="doi">10.1073/pnas.1324266111</pub-id><pub-id pub-id-type="pmid">24567377</pub-id></element-citation></ref><ref id="B100-diseases-04-00026"><label>100.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Weber</surname><given-names>F.</given-names></name><name><surname>Wagner</surname><given-names>V.</given-names></name><name><surname>Rasmussen</surname><given-names>S.B.</given-names></name><name><surname>Hartmann</surname><given-names>R.</given-names></name><name><surname>Paludan</surname><given-names>S.R.</given-names></name></person-group><article-title>Double-Stranded RNA Is Produced by Positive-Strand RNA Viruses and DNA Viruses but Not in Detectable Amounts by Negative-Strand RNA Viruses</article-title><source>J. Virol.</source><year>2006</year><volume>80</volume><fpage>5059</fpage><lpage>5064</lpage><pub-id pub-id-type="doi">10.1128/JVI.80.10.5059-5064.2006</pub-id><pub-id pub-id-type="pmid">16641297</pub-id></element-citation></ref><ref id="B101-diseases-04-00026"><label>101.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hemmi</surname><given-names>H.</given-names></name><name><surname>Takeuchi</surname><given-names>O.</given-names></name><name><surname>Kawai</surname><given-names>T.</given-names></name><name><surname>Kaisho</surname><given-names>T.</given-names></name><name><surname>Sato</surname><given-names>S.</given-names></name><name><surname>Sanjo</surname><given-names>H.</given-names></name><name><surname>Matsumoto</surname><given-names>M.</given-names></name><name><surname>Hoshino</surname><given-names>K.</given-names></name><name><surname>Wagner</surname><given-names>H.</given-names></name><name><surname>Takeda</surname><given-names>K.</given-names></name><etal></etal></person-group><article-title>A Toll-like receptor recognizes bacterial DNA</article-title><source>Nature</source><year>2000</year><volume>408</volume><fpage>740</fpage><lpage>745</lpage><pub-id pub-id-type="pmid">11130078</pub-id></element-citation></ref><ref id="B102-diseases-04-00026"><label>102.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Krug</surname><given-names>A.</given-names></name><name><surname>Luker</surname><given-names>G.D.</given-names></name><name><surname>Barchet</surname><given-names>W.</given-names></name><name><surname>Leib</surname><given-names>D.A.</given-names></name><name><surname>Akira</surname><given-names>S.</given-names></name><name><surname>Colonna</surname><given-names>M.</given-names></name></person-group><article-title>Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9</article-title><source>Blood</source><year>2003</year><volume>103</volume><fpage>1433</fpage><lpage>1437</lpage><pub-id pub-id-type="doi">10.1182/blood-2003-08-2674</pub-id><pub-id pub-id-type="pmid">14563635</pub-id></element-citation></ref><ref id="B103-diseases-04-00026"><label>103.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Krug</surname><given-names>A.</given-names></name><name><surname>French</surname><given-names>A.R.</given-names></name><name><surname>Barchet</surname><given-names>W.</given-names></name><name><surname>Fischer</surname><given-names>J.A.A.</given-names></name><name><surname>Dzionek</surname><given-names>A.</given-names></name><name><surname>Pingel</surname><given-names>J.T.</given-names></name><name><surname>Orihuela</surname><given-names>M.M.</given-names></name><name><surname>Akira</surname><given-names>S.</given-names></name><name><surname>Yokoyama</surname><given-names>W.M.</given-names></name><name><surname>Colonna</surname><given-names>M.</given-names></name></person-group><article-title>TLR9-Dependent Recognition of MCMV by IPC and DC Generates Coordinated Cytokine Responses that Activate Antiviral NK Cell Function</article-title><source>Immunity</source><year>2004</year><volume>21</volume><fpage>107</fpage><lpage>119</lpage><pub-id pub-id-type="doi">10.1016/j.immuni.2004.06.007</pub-id><pub-id pub-id-type="pmid">15345224</pub-id></element-citation></ref><ref id="B104-diseases-04-00026"><label>104.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hoffmann</surname><given-names>M.</given-names></name><name><surname>Zeisel</surname><given-names>M.B.</given-names></name><name><surname>Jilg</surname><given-names>N.</given-names></name><name><surname>Paranhos-Baccalà</surname><given-names>G.</given-names></name><name><surname>Stoll-Keller</surname><given-names>F.</given-names></name><name><surname>Wakita</surname><given-names>T.</given-names></name><name><surname>Hafkemeyer</surname><given-names>P.</given-names></name><name><surname>Blum</surname><given-names>H.E.</given-names></name><name><surname>Barth</surname><given-names>H.</given-names></name><name><surname>Henneke</surname><given-names>P.</given-names></name><etal></etal></person-group><article-title>Toll-like receptor 2 senses hepatitis C virus core protein but not infectious viral particles</article-title><source>J. Innate Immunity</source><year>2009</year><volume>1</volume><fpage>446</fpage><lpage>454</lpage><pub-id pub-id-type="doi">10.1159/000226136</pub-id><pub-id pub-id-type="pmid">20375602</pub-id></element-citation></ref><ref id="B105-diseases-04-00026"><label>105.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bieback</surname><given-names>K.</given-names></name><name><surname>Lien</surname><given-names>E.</given-names></name><name><surname>Klagge</surname><given-names>I.M.</given-names></name><name><surname>Avota</surname><given-names>E.</given-names></name><name><surname>Schneider-Schaulies</surname><given-names>J.</given-names></name><name><surname>Duprex</surname><given-names>W.P.</given-names></name><name><surname>Wagner</surname><given-names>H.</given-names></name><name><surname>Kirschning</surname><given-names>C.J.</given-names></name><name><surname>Ter Meulen</surname><given-names>V.</given-names></name><name><surname>Schneider-Schaulies</surname><given-names>S.</given-names></name></person-group><article-title>Hemagglutinin Protein of Wild-Type Measles Virus Activates Toll-Like Receptor 2 Signaling</article-title><source>J. Virol.</source><year>2002</year><volume>76</volume><fpage>8729</fpage><lpage>8736</lpage><pub-id pub-id-type="doi">10.1128/JVI.76.17.8729-8736.2002</pub-id><pub-id pub-id-type="pmid">12163593</pub-id></element-citation></ref><ref id="B106-diseases-04-00026"><label>106.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rallabhandi</surname><given-names>P.</given-names></name><name><surname>Phillips</surname><given-names>R.L.</given-names></name><name><surname>Boukhvalova</surname><given-names>M.S.</given-names></name><name><surname>Pletneva</surname><given-names>L.M.</given-names></name><name><surname>Shirey</surname><given-names>K.A.</given-names></name><name><surname>Gioannini</surname><given-names>T.L.</given-names></name><name><surname>Weiss</surname><given-names>J.P.</given-names></name><name><surname>Chow</surname><given-names>J.C.</given-names></name><name><surname>Hawkins</surname><given-names>L.D.</given-names></name><name><surname>Vogel</surname><given-names>S.N.</given-names></name><etal></etal></person-group><article-title>Respiratory Syncytial Virus Fusion Protein-Induced Toll-Like Receptor 4 (TLR4) Signaling Is Inhibited by the TLR4 Antagonists Rhodobacter sphaeroides Lipopolysaccharide and Eritoran (E5564) and Requires Direct Interaction with MD-2</article-title><source>mBio</source><year>2012</year><volume>3</volume><pub-id pub-id-type="doi">10.1128/mBio.00218-12</pub-id><pub-id pub-id-type="pmid">22872782</pub-id></element-citation></ref><ref id="B107-diseases-04-00026"><label>107.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ben Haij</surname><given-names>N.</given-names></name><name><surname>Leghmari</surname><given-names>K.</given-names></name><name><surname>Planès</surname><given-names>R.</given-names></name><name><surname>Thieblemont</surname><given-names>N.</given-names></name><name><surname>Bahraoui</surname><given-names>E.</given-names></name></person-group><article-title>HIV-1 Tat protein binds to TLR4-MD2 and signals to induce TNF-α and IL-10</article-title><source>Retrovirology</source><year>2013</year><volume>10</volume><fpage>1</fpage><lpage>12</lpage><pub-id pub-id-type="doi">10.1186/1742-4690-10-123</pub-id><pub-id pub-id-type="pmid">23289738</pub-id></element-citation></ref><ref id="B108-diseases-04-00026"><label>108.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kumar</surname><given-names>H.</given-names></name><name><surname>Kawai</surname><given-names>T.</given-names></name><name><surname>Akira</surname><given-names>S.</given-names></name></person-group><article-title>Toll-like receptors and innate immunity</article-title><source>Biochem. Biophys. Res. Commun.</source><year>2009</year><volume>388</volume><fpage>621</fpage><lpage>625</lpage><pub-id pub-id-type="doi">10.1016/j.bbrc.2009.08.062</pub-id><pub-id pub-id-type="pmid">19686699</pub-id></element-citation></ref><ref id="B109-diseases-04-00026"><label>109.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Honda</surname><given-names>K.</given-names></name><name><surname>Taniguchi</surname><given-names>T.</given-names></name></person-group><article-title>IRFs: Master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors</article-title><source>Nat. Rev. Immunol.</source><year>2006</year><volume>6</volume><fpage>644</fpage><lpage>658</lpage><pub-id pub-id-type="doi">10.1038/nri1900</pub-id><pub-id pub-id-type="pmid">16932750</pub-id></element-citation></ref><ref id="B110-diseases-04-00026"><label>110.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brown</surname><given-names>J.</given-names></name><name><surname>Wang</surname><given-names>H.</given-names></name><name><surname>Hajishengallis</surname><given-names>G.N.</given-names></name><name><surname>Martin</surname><given-names>M.</given-names></name></person-group><article-title>TLR-signaling Networks: An Integration of Adaptor Molecules, Kinases, and Cross-talk</article-title><source>J. Dent. Res.</source><year>2011</year><volume>90</volume><fpage>417</fpage><lpage>427</lpage><pub-id pub-id-type="doi">10.1177/0022034510381264</pub-id><pub-id pub-id-type="pmid">20940366</pub-id></element-citation></ref><ref id="B111-diseases-04-00026"><label>111.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>O’Neill</surname><given-names>L.A.J.</given-names></name><name><surname>Golenbock</surname><given-names>D.</given-names></name><name><surname>Bowie</surname><given-names>A.G.</given-names></name></person-group><article-title>The history of Toll-like receptors [mdash] redefining innate immunity</article-title><source>Nat. Rev. Immunol.</source><year>2013</year><volume>13</volume><fpage>453</fpage><lpage>460</lpage><pub-id pub-id-type="doi">10.1038/nri3446</pub-id><pub-id pub-id-type="pmid">23681101</pub-id></element-citation></ref><ref id="B112-diseases-04-00026"><label>112.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yoneyama</surname><given-names>M.</given-names></name><name><surname>Kikuchi</surname><given-names>M.</given-names></name><name><surname>Matsumoto</surname><given-names>K.</given-names></name><name><surname>Imaizumi</surname><given-names>T.</given-names></name><name><surname>Miyagishi</surname><given-names>M.</given-names></name><name><surname>Taira</surname><given-names>K.</given-names></name><name><surname>Foy</surname><given-names>E.</given-names></name><name><surname>Loo</surname><given-names>Y.M.</given-names></name><name><surname>Gale</surname><given-names>M.</given-names><suffix>Jr.</suffix></name><name><surname>Akira</surname><given-names>S.</given-names></name><etal></etal></person-group><article-title>Shared and Unique Functions of the DExD/H-Box Helicases RIG-I, MDA5, and LGP2 in Antiviral Innate Immunity</article-title><source>J. Immunol.</source><year>2005</year><volume>175</volume><fpage>2851</fpage><lpage>2858</lpage><pub-id pub-id-type="doi">10.4049/jimmunol.175.5.2851</pub-id><pub-id pub-id-type="pmid">16116171</pub-id></element-citation></ref><ref id="B113-diseases-04-00026"><label>113.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rodriguez</surname><given-names>K.R.</given-names></name><name><surname>Bruns</surname><given-names>A.M.</given-names></name><name><surname>Horvath</surname><given-names>C.M.</given-names></name></person-group><article-title>MDA5 and LGP2: Accomplices and Antagonists of Antiviral Signal Transduction</article-title><source>J. Virol.</source><year>2014</year><volume>88</volume><fpage>8194</fpage><lpage>8200</lpage><pub-id pub-id-type="doi">10.1128/JVI.00640-14</pub-id><pub-id pub-id-type="pmid">24850739</pub-id></element-citation></ref><ref id="B114-diseases-04-00026"><label>114.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Satoh</surname><given-names>T.</given-names></name><name><surname>Kato</surname><given-names>H.</given-names></name><name><surname>Kumagai</surname><given-names>Y.</given-names></name><name><surname>Yoneyama</surname><given-names>M.</given-names></name><name><surname>Sato</surname><given-names>S.</given-names></name><name><surname>Matsushita</surname><given-names>K.</given-names></name><name><surname>Tsujimura</surname><given-names>T.</given-names></name><name><surname>Fujita</surname><given-names>T.</given-names></name><name><surname>Akira</surname><given-names>S.</given-names></name><name><surname>Takeuchi</surname><given-names>O.</given-names></name></person-group><article-title>LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2010</year><volume>107</volume><fpage>1512</fpage><lpage>1517</lpage><pub-id pub-id-type="doi">10.1073/pnas.0912986107</pub-id><pub-id pub-id-type="pmid">20080593</pub-id></element-citation></ref><ref id="B115-diseases-04-00026"><label>115.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhu</surname><given-names>Z.</given-names></name><name><surname>Zhang</surname><given-names>X.</given-names></name><name><surname>Wang</surname><given-names>G.</given-names></name><name><surname>Zheng</surname><given-names>H.</given-names></name></person-group><article-title>The Laboratory of Genetics and Physiology 2: Emerging Insights into the Controversial Functions of This RIG-I-Like Receptor</article-title><source>BioMed Res. Int.</source><year>2014</year><volume>2014</volume><fpage>7</fpage><pub-id pub-id-type="doi">10.1155/2014/960190</pub-id><pub-id pub-id-type="pmid">24551857</pub-id></element-citation></ref><ref id="B116-diseases-04-00026"><label>116.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>G.</given-names></name><name><surname>Park</surname><given-names>H.-S.</given-names></name><name><surname>Pyo</surname><given-names>H.-M.</given-names></name><name><surname>Liu</surname><given-names>Q.</given-names></name><name><surname>Zhou</surname><given-names>Y.</given-names></name></person-group><article-title>Influenza A Virus Panhandle Structure Is Directly Involved in RIG-I Activation and Interferon Induction</article-title><source>J. Virol.</source><year>2015</year><volume>89</volume><fpage>6067</fpage><lpage>6079</lpage><pub-id pub-id-type="doi">10.1128/JVI.00232-15</pub-id><pub-id pub-id-type="pmid">25810557</pub-id></element-citation></ref><ref id="B117-diseases-04-00026"><label>117.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gack</surname><given-names>M.U.</given-names></name></person-group><article-title>Mechanisms of RIG-I-like Receptor Activation and Manipulation by Viral Pathogens</article-title><source>J. Virol.</source><year>2014</year><pub-id pub-id-type="doi">10.1128/JVI.03370-13</pub-id><pub-id pub-id-type="pmid">24623415</pub-id></element-citation></ref><ref id="B118-diseases-04-00026"><label>118.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kanneganti</surname><given-names>T.-D.</given-names></name></person-group><article-title>Central roles of NLRs and inflammasomes in viral infection</article-title><source>Nat. Rev. Immunol.</source><year>2010</year><volume>10</volume><fpage>688</fpage><lpage>698</lpage><pub-id pub-id-type="doi">10.1038/nri2851</pub-id><pub-id pub-id-type="pmid">20847744</pub-id></element-citation></ref><ref id="B119-diseases-04-00026"><label>119.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Guo</surname><given-names>H.</given-names></name><name><surname>Callaway</surname><given-names>J.B.</given-names></name><name><surname>Ting</surname><given-names>J.P.Y.</given-names></name></person-group><article-title>Inflammasomes: Mechanism of action, role in disease, and therapeutics</article-title><source>Nat. Med.</source><year>2015</year><volume>21</volume><fpage>677</fpage><lpage>687</lpage><pub-id pub-id-type="doi">10.1038/nm.3893</pub-id><pub-id pub-id-type="pmid">26121197</pub-id></element-citation></ref><ref id="B120-diseases-04-00026"><label>120.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ivashkiv</surname><given-names>L.B.</given-names></name><name><surname>Donlin</surname><given-names>L.T.</given-names></name></person-group><article-title>Regulation of type I interferon responses</article-title><source>Nat. Rev. Immunol.</source><year>2014</year><volume>14</volume><fpage>36</fpage><lpage>49</lpage><pub-id pub-id-type="doi">10.1038/nri3581</pub-id><pub-id pub-id-type="pmid">24362405</pub-id></element-citation></ref><ref id="B121-diseases-04-00026"><label>121.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schoggins</surname><given-names>J.W.</given-names></name><name><surname>Rice</surname><given-names>C.M.</given-names></name></person-group><article-title>Interferon-stimulated genes and their antiviral effector functions</article-title><source>Curr. Opin. Virol.</source><year>2011</year><volume>1</volume><fpage>519</fpage><lpage>525</lpage><pub-id pub-id-type="doi">10.1016/j.coviro.2011.10.008</pub-id><pub-id pub-id-type="pmid">22328912</pub-id></element-citation></ref><ref id="B122-diseases-04-00026"><label>122.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kindler</surname><given-names>E.</given-names></name><name><surname>Jónsdóttir</surname><given-names>H.R.</given-names></name><name><surname>Muth</surname><given-names>D.</given-names></name><name><surname>Hamming</surname><given-names>O.J.</given-names></name><name><surname>Hartmann</surname><given-names>R.</given-names></name><name><surname>Rodriguez</surname><given-names>R.</given-names></name><name><surname>Geffers</surname><given-names>R.</given-names></name><name><surname>Fouchier</surname><given-names>R.A.</given-names></name><name><surname>Drosten</surname><given-names>C.</given-names></name><name><surname>Müller</surname><given-names>M.A.</given-names></name><etal></etal></person-group><article-title>Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential</article-title><source>mBio</source><year>2013</year><volume>4</volume><fpage>e00611</fpage><lpage>e00612</lpage><pub-id pub-id-type="doi">10.1128/mBio.00611-12</pub-id><pub-id pub-id-type="pmid">23422412</pub-id></element-citation></ref><ref id="B123-diseases-04-00026"><label>123.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Frieman</surname><given-names>M.</given-names></name><name><surname>Heise</surname><given-names>M.</given-names></name><name><surname>Baric</surname><given-names>R.</given-names></name></person-group><article-title>SARS coronavirus and innate immunity</article-title><source>Virus Res.</source><year>2008</year><volume>133</volume><fpage>101</fpage><lpage>112</lpage><pub-id pub-id-type="doi">10.1016/j.virusres.2007.03.015</pub-id><pub-id pub-id-type="pmid">17451827</pub-id></element-citation></ref><ref id="B124-diseases-04-00026"><label>124.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Clementz</surname><given-names>M.A.</given-names></name><name><surname>Chen</surname><given-names>Z.</given-names></name><name><surname>Banach</surname><given-names>B.S.</given-names></name><name><surname>Wang</surname><given-names>Y.</given-names></name><name><surname>Sun</surname><given-names>L.</given-names></name><name><surname>Ratia</surname><given-names>K.</given-names></name><name><surname>Baez-Santos</surname><given-names>Y.M.</given-names></name><name><surname>Wang</surname><given-names>J.</given-names></name><name><surname>Takayama</surname><given-names>J.</given-names></name><name><surname>Ghosh</surname><given-names>A.K.</given-names></name><etal></etal></person-group><article-title>Deubiquitinating and Interferon Antagonism Activities of Coronavirus Papain-Like Proteases</article-title><source>J. Virol.</source><year>2010</year><volume>84</volume><fpage>4619</fpage><lpage>4629</lpage><pub-id pub-id-type="doi">10.1128/JVI.02406-09</pub-id><pub-id pub-id-type="pmid">20181693</pub-id></element-citation></ref><ref id="B125-diseases-04-00026"><label>125.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lau</surname><given-names>S.K.P.</given-names></name><name><surname>Lau</surname><given-names>C.C.Y.</given-names></name><name><surname>Chan</surname><given-names>K.-H.</given-names></name><name><surname>Li</surname><given-names>C.P.Y.</given-names></name><name><surname>Chen</surname><given-names>H.</given-names></name><name><surname>Jin</surname><given-names>D.-Y.</given-names></name><name><surname>Chan</surname><given-names>J.F.</given-names></name><name><surname>Woo</surname><given-names>P.C.</given-names></name><name><surname>Yuen</surname><given-names>K.Y.</given-names></name></person-group><article-title>Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: Implications for pathogenesis and treatment</article-title><source>J. Gen. Virol.</source><year>2013</year><volume>94</volume><fpage>2679</fpage><lpage>2690</lpage><pub-id pub-id-type="doi">10.1099/vir.0.055533-0</pub-id><pub-id pub-id-type="pmid">24077366</pub-id></element-citation></ref><ref id="B126-diseases-04-00026"><label>126.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cheung</surname><given-names>C.Y.</given-names></name><name><surname>Poon</surname><given-names>L.L.M.</given-names></name><name><surname>Ng</surname><given-names>I.H.Y.</given-names></name><name><surname>Luk</surname><given-names>W.</given-names></name><name><surname>Sia</surname><given-names>S.-F.</given-names></name><name><surname>Wu</surname><given-names>M.H.S.</given-names></name><name><surname>Chan</surname><given-names>K.H.</given-names></name><name><surname>Yuen</surname><given-names>K.Y.</given-names></name><name><surname>Gordon</surname><given-names>S.</given-names></name><name><surname>Guan</surname><given-names>Y.</given-names></name><etal></etal></person-group><article-title>Cytokine Responses in Severe Acute Respiratory Syndrome Coronavirus-Infected Macrophages In Vitro: Possible Relevance to Pathogenesis</article-title><source>J. Virol.</source><year>2005</year><volume>79</volume><fpage>7819</fpage><lpage>7826</lpage><pub-id pub-id-type="doi">10.1128/JVI.79.12.7819-7826.2005</pub-id><pub-id pub-id-type="pmid">15919935</pub-id></element-citation></ref><ref id="B127-diseases-04-00026"><label>127.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Randall</surname><given-names>R.E.</given-names></name><name><surname>Goodbourn</surname><given-names>S.</given-names></name></person-group><article-title>Interferons and viruses: An interplay between induction, signalling, antiviral responses and virus countermeasures</article-title><source>J. Gen. Virol.</source><year>2008</year><volume>89</volume><fpage>1</fpage><lpage>47</lpage><pub-id pub-id-type="doi">10.1099/vir.0.83391-0</pub-id><pub-id pub-id-type="pmid">18089727</pub-id></element-citation></ref><ref id="B128-diseases-04-00026"><label>128.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Funk</surname><given-names>C.J.</given-names></name><name><surname>Wang</surname><given-names>J.</given-names></name><name><surname>Ito</surname><given-names>Y.</given-names></name><name><surname>Travanty</surname><given-names>E.A.</given-names></name><name><surname>Voelker</surname><given-names>D.R.</given-names></name><name><surname>Holmes</surname><given-names>K.V.</given-names></name><name><surname>Mason</surname><given-names>R.J.</given-names></name></person-group><article-title>Infection of human alveolar macrophages by human coronavirus strain 229E</article-title><source>J. Gen. Virol.</source><year>2012</year><volume>93</volume><fpage>494</fpage><lpage>503</lpage><pub-id pub-id-type="doi">10.1099/vir.0.038414-0</pub-id><pub-id pub-id-type="pmid">22090214</pub-id></element-citation></ref><ref id="B129-diseases-04-00026"><label>129.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gosert</surname><given-names>R.</given-names></name><name><surname>Kanjanahaluethai</surname><given-names>A.</given-names></name><name><surname>Egger</surname><given-names>D.</given-names></name><name><surname>Bienz</surname><given-names>K.</given-names></name><name><surname>Baker</surname><given-names>S.C.</given-names></name></person-group><article-title>RNA Replication of Mouse Hepatitis Virus Takes Place at Double-Membrane Vesicles</article-title><source>J. Virol.</source><year>2002</year><volume>76</volume><fpage>3697</fpage><lpage>3708</lpage><pub-id pub-id-type="doi">10.1128/JVI.76.8.3697-3708.2002</pub-id><pub-id pub-id-type="pmid">11907209</pub-id></element-citation></ref><ref id="B130-diseases-04-00026"><label>130.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Perlman</surname><given-names>S.</given-names></name><name><surname>Netland</surname><given-names>J.</given-names></name></person-group><article-title>Coronaviruses post-SARS: Update on replication and pathogenesis. Nature reviews</article-title><source>Microbiology</source><year>2009</year><volume>7</volume><fpage>439</fpage><lpage>450</lpage><pub-id pub-id-type="pmid">19430490</pub-id></element-citation></ref><ref id="B131-diseases-04-00026"><label>131.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Siu</surname><given-names>K.L.</given-names></name><name><surname>Kok</surname><given-names>K.H.</given-names></name><name><surname>Ng</surname><given-names>M.H.</given-names></name><name><surname>Poon</surname><given-names>V.K.</given-names></name><name><surname>Yuen</surname><given-names>K.Y.</given-names></name><name><surname>Zheng</surname><given-names>B.J.</given-names></name><name><surname>Jin</surname><given-names>D.Y.</given-names></name></person-group><article-title>Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKε Complex</article-title><source>J. Biol. Chem.</source><year>2009</year><volume>284</volume><fpage>16202</fpage><lpage>16209</lpage><pub-id pub-id-type="doi">10.1074/jbc.M109.008227</pub-id><pub-id pub-id-type="pmid">19380580</pub-id></element-citation></ref><ref id="B132-diseases-04-00026"><label>132.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Siu</surname><given-names>K.-L.</given-names></name><name><surname>Chan</surname><given-names>C.-P.</given-names></name><name><surname>Kok</surname><given-names>K.-H.</given-names></name><name><surname>Chiu-Yat Woo</surname><given-names>P.</given-names></name><name><surname>Jin</surname><given-names>D.-Y.</given-names></name></person-group><article-title>Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain</article-title><source>Cell. Mol. Immunol.</source><year>2014</year><volume>11</volume><fpage>141</fpage><lpage>149</lpage><pub-id pub-id-type="doi">10.1038/cmi.2013.61</pub-id><pub-id pub-id-type="pmid">24509444</pub-id></element-citation></ref><ref id="B133-diseases-04-00026"><label>133.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>Y.</given-names></name><name><surname>Zhang</surname><given-names>L.</given-names></name><name><surname>Geng</surname><given-names>H.</given-names></name><name><surname>Deng</surname><given-names>Y.</given-names></name><name><surname>Huang</surname><given-names>B.</given-names></name><name><surname>Guo</surname><given-names>Y.</given-names></name><name><surname>Zhao</surname><given-names>Z.</given-names></name><name><surname>Tan</surname><given-names>W.</given-names></name></person-group><article-title>The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists</article-title><source>Protein Cell</source><year>2013</year><volume>4</volume><fpage>951</fpage><lpage>961</lpage><pub-id pub-id-type="doi">10.1007/s13238-013-3096-8</pub-id><pub-id pub-id-type="pmid">24318862</pub-id></element-citation></ref><ref id="B134-diseases-04-00026"><label>134.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kopecky-Bromberg</surname><given-names>S.A.</given-names></name><name><surname>Martínez-Sobrido</surname><given-names>L.</given-names></name><name><surname>Frieman</surname><given-names>M.</given-names></name><name><surname>Baric</surname><given-names>R.A.</given-names></name><name><surname>Palese</surname><given-names>P.</given-names></name></person-group><article-title>Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame (ORF) 3b, ORF 6, and Nucleocapsid Proteins Function as Interferon Antagonists</article-title><source>J. Virol.</source><year>2007</year><volume>81</volume><fpage>548</fpage><lpage>557</lpage><pub-id pub-id-type="doi">10.1128/JVI.01782-06</pub-id><pub-id pub-id-type="pmid">17108024</pub-id></element-citation></ref><ref id="B135-diseases-04-00026"><label>135.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lu</surname><given-names>X.</given-names></name><name><surname>Pan</surname><given-names>J.A.</given-names></name><name><surname>Tao</surname><given-names>J.</given-names></name><name><surname>Guo</surname><given-names>D.</given-names></name></person-group><article-title>SARS-CoV nucleocapsid protein antagonizes IFN-β response by targeting initial step of IFN-β induction pathway, and its C-terminal region is critical for the antagonism</article-title><source>Virus Genes</source><year>2010</year><volume>42</volume><fpage>37</fpage><lpage>45</lpage><pub-id pub-id-type="doi">10.1007/s11262-010-0544-x</pub-id><pub-id pub-id-type="pmid">20976535</pub-id></element-citation></ref><ref id="B136-diseases-04-00026"><label>136.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>C.</given-names></name><name><surname>Lokugamage</surname><given-names>K.G.</given-names></name><name><surname>Rozovics</surname><given-names>J.M.</given-names></name><name><surname>Narayanan</surname><given-names>K.</given-names></name><name><surname>Semler</surname><given-names>B.L.</given-names></name><name><surname>Makino</surname><given-names>S.</given-names></name></person-group><article-title>SARS Coronavirus nsp1 Protein Induces Template-Dependent Endonucleolytic Cleavage of mRNAs: Viral mRNAs Are Resistant to nsp1-Induced RNA Cleavage</article-title><source>PLoS Pathog.</source><year>2011</year><volume>7</volume><elocation-id>e1002433</elocation-id><pub-id pub-id-type="doi">10.1371/journal.ppat.1002433</pub-id><pub-id pub-id-type="pmid">22174690</pub-id></element-citation></ref><ref id="B137-diseases-04-00026"><label>137.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lokugamage</surname><given-names>K.G.</given-names></name><name><surname>Narayanan</surname><given-names>K.</given-names></name><name><surname>Nakagawa</surname><given-names>K.</given-names></name><name><surname>Terasaki</surname><given-names>K.</given-names></name><name><surname>Ramirez</surname><given-names>S.I.</given-names></name><name><surname>Tseng</surname><given-names>C.-T.K.</given-names></name><name><surname>Ramirez</surname><given-names>S.I.</given-names></name><name><surname>Tseng</surname><given-names>C.T.</given-names></name><name><surname>Makino</surname><given-names>S.</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus nsp1 inhibits host gene expression by selectively targeting nuclear-transcribed mRNAs but spares mRNAs of cytoplasmic origin</article-title><source>J. Virol.</source><year>2015</year><pub-id pub-id-type="doi">10.1128/JVI.01352-15</pub-id><pub-id pub-id-type="pmid">26311885</pub-id></element-citation></ref><ref id="B138-diseases-04-00026"><label>138.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jauregui</surname><given-names>A.R.</given-names></name><name><surname>Savalia</surname><given-names>D.</given-names></name><name><surname>Lowry</surname><given-names>V.K.</given-names></name><name><surname>Farrell</surname><given-names>C.M.</given-names></name><name><surname>Wathelet</surname><given-names>M.G.</given-names></name></person-group><article-title>Identification of Residues of SARS-CoV nsp1 That Differentially Affect Inhibition of Gene Expression and Antiviral Signaling</article-title><source>PLoS ONE</source><year>2013</year><volume>8</volume><elocation-id>e62416</elocation-id><pub-id pub-id-type="doi">10.1371/journal.pone.0062416</pub-id><pub-id pub-id-type="pmid">23658627</pub-id></element-citation></ref><ref id="B139-diseases-04-00026"><label>139.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mielech</surname><given-names>A.M.</given-names></name><name><surname>Kilianski</surname><given-names>A.</given-names></name><name><surname>Baez-Santos</surname><given-names>Y.M.</given-names></name><name><surname>Mesecar</surname><given-names>A.D.</given-names></name><name><surname>Baker</surname><given-names>S.C.</given-names></name></person-group><article-title>MERS-CoV papain-like protease has deISGylating and deubiquitinating activities</article-title><source>Virology</source><year>2014</year><volume>450–451</volume><fpage>64</fpage><lpage>70</lpage><pub-id pub-id-type="doi">10.1016/j.virol.2013.11.040</pub-id><pub-id pub-id-type="pmid">24503068</pub-id></element-citation></ref><ref id="B140-diseases-04-00026"><label>140.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Devaraj</surname><given-names>S.G.</given-names></name><name><surname>Wang</surname><given-names>N.</given-names></name><name><surname>Chen</surname><given-names>Z.</given-names></name><name><surname>Chen</surname><given-names>Z.</given-names></name><name><surname>Tseng</surname><given-names>M.</given-names></name><name><surname>Barretto</surname><given-names>N.</given-names></name><name><surname>Lin</surname><given-names>R.</given-names></name><name><surname>Peters</surname><given-names>C.J.</given-names></name><name><surname>Tseng</surname><given-names>C.T.</given-names></name><name><surname>Baker</surname><given-names>S.C.</given-names></name><etal></etal></person-group><article-title>Regulation of IRF-3 dependent innate immunity by the papain-like protease domain of the sars coronavirus</article-title><source>J. Biol. Chem.</source><year>2007</year><volume>282</volume><fpage>32208</fpage><lpage>32221</lpage><pub-id pub-id-type="doi">10.1074/jbc.M704870200</pub-id><pub-id pub-id-type="pmid">17761676</pub-id></element-citation></ref><ref id="B141-diseases-04-00026"><label>141.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>X.</given-names></name><name><surname>Chen</surname><given-names>X.</given-names></name><name><surname>Bian</surname><given-names>G.</given-names></name><name><surname>Tu</surname><given-names>J.</given-names></name><name><surname>Xing</surname><given-names>Y.</given-names></name><name><surname>Wang</surname><given-names>Y.</given-names></name><name><surname>Chen</surname><given-names>Z.</given-names></name></person-group><article-title>Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease</article-title><source>J. Gen. Virol.</source><year>2014</year><volume>95</volume><fpage>614</fpage><lpage>626</lpage><pub-id pub-id-type="doi">10.1099/vir.0.059014-0</pub-id><pub-id pub-id-type="pmid">24362959</pub-id></element-citation></ref><ref id="B142-diseases-04-00026"><label>142.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kuri</surname><given-names>T.</given-names></name><name><surname>Eriksson</surname><given-names>K.K.</given-names></name><name><surname>Putics</surname><given-names>A.</given-names></name><name><surname>Züst</surname><given-names>R.</given-names></name><name><surname>Snijder</surname><given-names>E.J.</given-names></name><name><surname>Davidson</surname><given-names>A.D.</given-names></name><name><surname>Siddell</surname><given-names>S.G.</given-names></name><name><surname>Thiel</surname><given-names>V.</given-names></name><name><surname>Ziebuhr</surname><given-names>J.</given-names></name><name><surname>Weber</surname><given-names>F.</given-names></name></person-group><article-title>The ADP-ribose-1′′-monophosphatase domains of severe acute respiratory syndrome coronavirus and human coronavirus 229E mediate resistance to antiviral interferon responses</article-title><source>J. Gen. Virol.</source><year>2011</year><volume>92</volume><fpage>1899</fpage><lpage>1905</lpage><pub-id pub-id-type="doi">10.1099/vir.0.031856-0</pub-id><pub-id pub-id-type="pmid">21525212</pub-id></element-citation></ref><ref id="B143-diseases-04-00026"><label>143.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stevens</surname><given-names>F.J.</given-names></name><name><surname>Argon</surname><given-names>Y.</given-names></name></person-group><article-title>Protein folding in the ER</article-title><source>Semin. Cell Dev. Biol.</source><year>1999</year><volume>10</volume><fpage>443</fpage><lpage>454</lpage><pub-id pub-id-type="doi">10.1006/scdb.1999.0315</pub-id><pub-id pub-id-type="pmid">10597627</pub-id></element-citation></ref><ref id="B144-diseases-04-00026"><label>144.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ron</surname><given-names>D.</given-names></name><name><surname>Walter</surname><given-names>P.</given-names></name></person-group><article-title>Signal integration in the endoplasmic reticulum unfolded protein response</article-title><source>Nat. Rev. Mol. Cell Biol.</source><year>2007</year><volume>8</volume><fpage>519</fpage><lpage>529</lpage><pub-id pub-id-type="doi">10.1038/nrm2199</pub-id><pub-id pub-id-type="pmid">17565364</pub-id></element-citation></ref><ref id="B145-diseases-04-00026"><label>145.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fung</surname><given-names>T.S.</given-names></name><name><surname>Liu</surname><given-names>D.X.</given-names></name></person-group><article-title>Coronavirus infection, ER stress, apoptosis and innate immunity</article-title><source>Front. Microbiol.</source><year>2014</year><volume>5</volume><fpage>296</fpage><pub-id pub-id-type="doi">10.3389/fmicb.2014.00296</pub-id><pub-id pub-id-type="pmid">24987391</pub-id></element-citation></ref><ref id="B146-diseases-04-00026"><label>146.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Teske</surname><given-names>B.F.</given-names></name><name><surname>Wek</surname><given-names>S.A.</given-names></name><name><surname>Bunpo</surname><given-names>P.</given-names></name><name><surname>Cundiff</surname><given-names>J.K.</given-names></name><name><surname>McClintick</surname><given-names>J.N.</given-names></name><name><surname>Anthony</surname><given-names>T.G.</given-names></name><name><surname>Wek</surname><given-names>R.C.</given-names></name></person-group><article-title>The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress</article-title><source>Mol. Biol. Cell</source><year>2011</year><volume>22</volume><fpage>4390</fpage><lpage>4405</lpage><pub-id pub-id-type="doi">10.1091/mbc.E11-06-0510</pub-id><pub-id pub-id-type="pmid">21917591</pub-id></element-citation></ref><ref id="B147-diseases-04-00026"><label>147.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Harding</surname><given-names>H.P.</given-names></name><name><surname>Zhang</surname><given-names>Y.</given-names></name><name><surname>Bertolotti</surname><given-names>A.</given-names></name><name><surname>Zeng</surname><given-names>H.</given-names></name><name><surname>Ron</surname><given-names>D.</given-names></name></person-group><article-title><italic>Perk</italic> Is Essential for Translational Regulation and Cell Survival during the Unfolded Protein Response</article-title><source>Mol. Cell</source><year>2000</year><volume>5</volume><fpage>897</fpage><lpage>904</lpage><pub-id pub-id-type="doi">10.1016/S1097-2765(00)80330-5</pub-id><pub-id pub-id-type="pmid">10882126</pub-id></element-citation></ref><ref id="B148-diseases-04-00026"><label>148.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Harding</surname><given-names>H.P.</given-names></name><name><surname>Novoa</surname><given-names>I.</given-names></name><name><surname>Zhang</surname><given-names>Y.</given-names></name><name><surname>Zeng</surname><given-names>H.</given-names></name><name><surname>Wek</surname><given-names>R.</given-names></name><name><surname>Schapira</surname><given-names>M.</given-names></name><name><surname>Ron</surname><given-names>D.</given-names></name></person-group><article-title>Regulated Translation Initiation Controls Stress-Induced Gene Expression in Mammalian Cells</article-title><source>Mol. Cell</source><year>2000</year><volume>6</volume><fpage>1099</fpage><lpage>1108</lpage><pub-id pub-id-type="doi">10.1016/S1097-2765(00)00108-8</pub-id><pub-id pub-id-type="pmid">11106749</pub-id></element-citation></ref><ref id="B149-diseases-04-00026"><label>149.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oyadomari</surname><given-names>S.</given-names></name><name><surname>Mori</surname><given-names>M.</given-names></name></person-group><article-title>Roles of CHOP//GADD153 in endoplasmic reticulum stress</article-title><source>Cell Death Differ.</source><year>2003</year><volume>11</volume><fpage>381</fpage><lpage>389</lpage><pub-id pub-id-type="doi">10.1038/sj.cdd.4401373</pub-id><pub-id pub-id-type="pmid">14685163</pub-id></element-citation></ref><ref id="B150-diseases-04-00026"><label>150.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fung</surname><given-names>T.S.</given-names></name><name><surname>Huang</surname><given-names>M.</given-names></name><name><surname>Liu</surname><given-names>D.X.</given-names></name></person-group><article-title>Coronavirus-induced ER stress response and its involvement in regulation of coronavirus-host interactions</article-title><source>Virus Res.</source><year>2014</year><volume>194</volume><fpage>110</fpage><lpage>123</lpage><pub-id pub-id-type="doi">10.1016/j.virusres.2014.09.016</pub-id><pub-id pub-id-type="pmid">25304691</pub-id></element-citation></ref><ref id="B151-diseases-04-00026"><label>151.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Minakshi</surname><given-names>R.</given-names></name><name><surname>Padhan</surname><given-names>K.</given-names></name><name><surname>Rani</surname><given-names>M.</given-names></name><name><surname>Khan</surname><given-names>N.</given-names></name><name><surname>Ahmad</surname><given-names>F.</given-names></name><name><surname>Jameel</surname><given-names>S.</given-names></name></person-group><article-title>The SARS Coronavirus 3a Protein Causes Endoplasmic Reticulum Stress and Induces Ligand-Independent Downregulation of the Type 1 Interferon Receptor</article-title><source>PLoS ONE</source><year>2009</year><volume>4</volume><elocation-id>e8342</elocation-id><pub-id pub-id-type="doi">10.1371/journal.pone.0008342</pub-id><pub-id pub-id-type="pmid">20020050</pub-id></element-citation></ref><ref id="B152-diseases-04-00026"><label>152.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chan</surname><given-names>C.-P.</given-names></name><name><surname>Siu</surname><given-names>K.-L.</given-names></name><name><surname>Chin</surname><given-names>K.-T.</given-names></name><name><surname>Yuen</surname><given-names>K.-Y.</given-names></name><name><surname>Zheng</surname><given-names>B.</given-names></name><name><surname>Jin</surname><given-names>D.-Y.</given-names></name></person-group><article-title>Modulation of the Unfolded Protein Response by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein</article-title><source>J. Virol.</source><year>2006</year><volume>80</volume><fpage>9279</fpage><lpage>9287</lpage><pub-id pub-id-type="doi">10.1128/JVI.00659-06</pub-id><pub-id pub-id-type="pmid">16940539</pub-id></element-citation></ref><ref id="B153-diseases-04-00026"><label>153.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Siu</surname><given-names>K.-L.</given-names></name><name><surname>Chan</surname><given-names>C.-P.</given-names></name><name><surname>Kok</surname><given-names>K.-H.</given-names></name><name><surname>C-Y Woo</surname><given-names>P.</given-names></name><name><surname>Jin</surname><given-names>D.-Y.</given-names></name></person-group><article-title>Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1</article-title><source>Cell Biosci.</source><year>2014</year><volume>4</volume><fpage>1</fpage><lpage>9</lpage><pub-id pub-id-type="doi">10.1186/2045-3701-4-3</pub-id><pub-id pub-id-type="pmid">24383941</pub-id></element-citation></ref><ref id="B154-diseases-04-00026"><label>154.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liao</surname><given-names>Y.</given-names></name><name><surname>Fung</surname><given-names>T.S.</given-names></name><name><surname>Huang</surname><given-names>M.</given-names></name><name><surname>Fang</surname><given-names>S.G.</given-names></name><name><surname>Zhong</surname><given-names>Y.</given-names></name><name><surname>Liu</surname><given-names>D.X.</given-names></name></person-group><article-title>Upregulation of CHOP/GADD153 during Coronavirus Infectious Bronchitis Virus Infection Modulates Apoptosis by Restricting Activation of the Extracellular Signal-Regulated Kinase Pathway</article-title><source>J. Virol.</source><year>2013</year><volume>87</volume><fpage>8124</fpage><lpage>8134</lpage><pub-id pub-id-type="doi">10.1128/JVI.00626-13</pub-id><pub-id pub-id-type="pmid">23678184</pub-id></element-citation></ref><ref id="B155-diseases-04-00026"><label>155.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>X.</given-names></name><name><surname>Liao</surname><given-names>Y.</given-names></name><name><surname>Yap</surname><given-names>P.L.</given-names></name><name><surname>Png</surname><given-names>K.J.</given-names></name><name><surname>Tam</surname><given-names>J.P.</given-names></name><name><surname>Liu</surname><given-names>D.X.</given-names></name></person-group><article-title>Inhibition of Protein Kinase R Activation and Upregulation of GADD34 Expression Play a Synergistic Role in Facilitating Coronavirus Replication by Maintaining De Novo Protein Synthesis in Virus-Infected Cells</article-title><source>J. Virol.</source><year>2009</year><volume>83</volume><fpage>12462</fpage><lpage>12472</lpage><pub-id pub-id-type="doi">10.1128/JVI.01546-09</pub-id><pub-id pub-id-type="pmid">19776135</pub-id></element-citation></ref><ref id="B156-diseases-04-00026"><label>156.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hong</surname><given-names>M.</given-names></name><name><surname>Luo</surname><given-names>S.</given-names></name><name><surname>Baumeister</surname><given-names>P.</given-names></name><name><surname>Huang</surname><given-names>J.-M.</given-names></name><name><surname>Gogia</surname><given-names>R.K.</given-names></name><name><surname>Li</surname><given-names>M.</given-names></name><name><surname>Lee</surname><given-names>A.S.</given-names></name></person-group><article-title>Underglycosylation of ATF6 as a Novel Sensing Mechanism for Activation of the Unfolded Protein Response</article-title><source>J. Biol. Chem.</source><year>2004</year><volume>279</volume><fpage>11354</fpage><lpage>11363</lpage><pub-id pub-id-type="doi">10.1074/jbc.M309804200</pub-id><pub-id pub-id-type="pmid">14699159</pub-id></element-citation></ref><ref id="B157-diseases-04-00026"><label>157.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nadanaka</surname><given-names>S.</given-names></name><name><surname>Okada</surname><given-names>T.</given-names></name><name><surname>Yoshida</surname><given-names>H.</given-names></name><name><surname>Mori</surname><given-names>K.</given-names></name></person-group><article-title>Role of Disulfide Bridges Formed in the Luminal Domain of ATF6 in Sensing Endoplasmic Reticulum Stress</article-title><source>Mol. Cell. Biol.</source><year>2007</year><volume>27</volume><fpage>1027</fpage><lpage>1043</lpage><pub-id pub-id-type="doi">10.1128/MCB.00408-06</pub-id><pub-id pub-id-type="pmid">17101776</pub-id></element-citation></ref><ref id="B158-diseases-04-00026"><label>158.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schröder</surname><given-names>M.</given-names></name><name><surname>Kaufman</surname><given-names>R.J.</given-names></name></person-group><article-title>The mammalian unfolded protein response</article-title><source>Annu. Rev. Biochem.</source><year>2005</year><volume>74</volume><fpage>739</fpage><lpage>789</lpage><pub-id pub-id-type="doi">10.1146/annurev.biochem.73.011303.074134</pub-id><pub-id pub-id-type="pmid">15952902</pub-id></element-citation></ref><ref id="B159-diseases-04-00026"><label>159.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yoshida</surname><given-names>H.</given-names></name><name><surname>Matsui</surname><given-names>T.</given-names></name><name><surname>Yamamoto</surname><given-names>A.</given-names></name><name><surname>Okada</surname><given-names>T.</given-names></name><name><surname>Mori</surname><given-names>K.</given-names></name></person-group><article-title>XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor</article-title><source>Cell</source><year>2001</year><volume>107</volume><fpage>881</fpage><lpage>891</lpage><pub-id pub-id-type="doi">10.1016/S0092-8674(01)00611-0</pub-id><pub-id pub-id-type="pmid">11779464</pub-id></element-citation></ref><ref id="B160-diseases-04-00026"><label>160.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sung</surname><given-names>S.-C.</given-names></name><name><surname>Chao</surname><given-names>C.-Y.</given-names></name><name><surname>Jeng</surname><given-names>K.-S.</given-names></name><name><surname>Yang</surname><given-names>J.-Y.</given-names></name><name><surname>Lai</surname><given-names>M.M.C.</given-names></name></person-group><article-title>The 8ab protein of SARS-CoV is a luminal ER membrane-associated protein and induces the activation of ATF6</article-title><source>Virology</source><year>2009</year><volume>387</volume><fpage>402</fpage><lpage>413</lpage><pub-id pub-id-type="doi">10.1016/j.virol.2009.02.021</pub-id><pub-id pub-id-type="pmid">19304306</pub-id></element-citation></ref><ref id="B161-diseases-04-00026"><label>161.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oostra</surname><given-names>M.</given-names></name><name><surname>de Haan</surname><given-names>C.A.M.</given-names></name><name><surname>Rottier</surname><given-names>P.J.M.</given-names></name></person-group><article-title>The 29-Nucleotide Deletion Present in Human but Not in Animal Severe Acute Respiratory Syndrome Coronaviruses Disrupts the Functional Expression of Open Reading Frame 8</article-title><source>J. Virol.</source><year>2007</year><volume>81</volume><fpage>13876</fpage><lpage>13888</lpage><pub-id pub-id-type="doi">10.1128/JVI.01631-07</pub-id><pub-id pub-id-type="pmid">17928347</pub-id></element-citation></ref><ref id="B162-diseases-04-00026"><label>162.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Szegezdi</surname><given-names>E.</given-names></name><name><surname>Logue</surname><given-names>S.E.</given-names></name><name><surname>Gorman</surname><given-names>A.M.</given-names></name><name><surname>Samali</surname><given-names>A.</given-names></name></person-group><article-title>Mediators of endoplasmic reticulum stress-induced apoptosis</article-title><source>EMBO Rep.</source><year>2006</year><volume>7</volume><fpage>880</fpage><lpage>885</lpage><pub-id pub-id-type="doi">10.1038/sj.embor.7400779</pub-id><pub-id pub-id-type="pmid">16953201</pub-id></element-citation></ref><ref id="B163-diseases-04-00026"><label>163.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mori</surname><given-names>K.</given-names></name></person-group><article-title>Signalling Pathways in the Unfolded Protein Response: Development from Yeast to Mammals</article-title><source>J. Biochem.</source><year>2009</year><volume>146</volume><fpage>743</fpage><lpage>750</lpage><pub-id pub-id-type="doi">10.1093/jb/mvp166</pub-id><pub-id pub-id-type="pmid">19861400</pub-id></element-citation></ref><ref id="B164-diseases-04-00026"><label>164.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Credle</surname><given-names>J.J.</given-names></name><name><surname>Finer-Moore</surname><given-names>J.S.</given-names></name><name><surname>Papa</surname><given-names>F.R.</given-names></name><name><surname>Stroud</surname><given-names>R.M.</given-names></name><name><surname>Walter</surname><given-names>P.</given-names></name></person-group><article-title>On the mechanism of sensing unfolded protein in the endoplasmic reticulum</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2005</year><volume>102</volume><fpage>18773</fpage><lpage>18784</lpage><pub-id pub-id-type="doi">10.1073/pnas.0509487102</pub-id><pub-id pub-id-type="pmid">16365312</pub-id></element-citation></ref><ref id="B165-diseases-04-00026"><label>165.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gardner</surname><given-names>B.M.</given-names></name><name><surname>Walter</surname><given-names>P.</given-names></name></person-group><article-title>Unfolded Proteins Are Ire1-Activating Ligands That Directly Induce the Unfolded Protein Response</article-title><source>Science</source><year>2011</year><volume>333</volume><fpage>1891</fpage><lpage>1894</lpage><pub-id pub-id-type="doi">10.1126/science.1209126</pub-id><pub-id pub-id-type="pmid">21852455</pub-id></element-citation></ref><ref id="B166-diseases-04-00026"><label>166.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Prischi</surname><given-names>F.</given-names></name><name><surname>Nowak</surname><given-names>P.R.</given-names></name><name><surname>Carrara</surname><given-names>M.</given-names></name><name><surname>Ali</surname><given-names>M.M.U.</given-names></name></person-group><article-title>Phosphoregulation of Ire1 RNase splicing activity</article-title><source>Nat. Commun.</source><year>2014</year><volume>5</volume><pub-id pub-id-type="doi">10.1038/ncomms4554</pub-id><pub-id pub-id-type="pmid">24704861</pub-id></element-citation></ref><ref id="B167-diseases-04-00026"><label>167.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gao</surname><given-names>B.</given-names></name><name><surname>Lee</surname><given-names>S.-M.</given-names></name><name><surname>Chen</surname><given-names>A.</given-names></name><name><surname>Zhang</surname><given-names>J.</given-names></name><name><surname>Zhang</surname><given-names>D.D.</given-names></name><name><surname>Kannan</surname><given-names>K.</given-names></name><name><surname>Ortmann</surname><given-names>R.A.</given-names></name><name><surname>Fang</surname><given-names>D.</given-names></name></person-group><article-title>Synoviolin promotes IRE1 ubiquitination and degradation in synovial fibroblasts from mice with collagen-induced arthritis</article-title><source>EMBO Rep.</source><year>2008</year><volume>9</volume><fpage>480</fpage><lpage>485</lpage><pub-id pub-id-type="doi">10.1038/embor.2008.37</pub-id><pub-id pub-id-type="pmid">18369366</pub-id></element-citation></ref><ref id="B168-diseases-04-00026"><label>168.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yoshida</surname><given-names>H.</given-names></name><name><surname>Oku</surname><given-names>M.</given-names></name><name><surname>Suzuki</surname><given-names>M.</given-names></name><name><surname>Mori</surname><given-names>K.</given-names></name></person-group><article-title>pXBP1(U) encoded in XBP1 pre-mRNA negatively regulates unfolded protein response activator pXBP1(S) in mammalian ER stress response</article-title><source>J. Cell Biol.</source><year>2006</year><volume>172</volume><fpage>565</fpage><lpage>575</lpage><pub-id pub-id-type="doi">10.1083/jcb.200508145</pub-id><pub-id pub-id-type="pmid">16461360</pub-id></element-citation></ref><ref id="B169-diseases-04-00026"><label>169.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tam</surname><given-names>A.B.</given-names></name><name><surname>Koong</surname><given-names>A.C.</given-names></name><name><surname>Niwa</surname><given-names>M.</given-names></name></person-group><article-title>Ire1 Has Distinct Catalytic Mechanisms for <italic>XBP1/HAC1</italic> Splicing and RIDD</article-title><source>Cell Rep.</source><year>2014</year><volume>9</volume><fpage>850</fpage><lpage>858</lpage><pub-id pub-id-type="pmid">25437541</pub-id></element-citation></ref><ref id="B170-diseases-04-00026"><label>170.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Walter</surname><given-names>F.</given-names></name><name><surname>Schmid</surname><given-names>J.</given-names></name><name><surname>Dussmann</surname><given-names>H.</given-names></name><name><surname>Concannon</surname><given-names>C.G.</given-names></name><name><surname>Prehn</surname><given-names>J.H.M.</given-names></name></person-group><article-title>Imaging of single cell responses to ER stress indicates that the relative dynamics of IRE1/XBP1 and PERK/ATF4 signalling rather than a switch between signalling branches determine cell survival</article-title><source>Cell Death Differ.</source><year>2015</year><volume>22</volume><fpage>1502</fpage><lpage>1516</lpage><pub-id pub-id-type="doi">10.1038/cdd.2014.241</pub-id><pub-id pub-id-type="pmid">25633195</pub-id></element-citation></ref><ref id="B171-diseases-04-00026"><label>171.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Urano</surname><given-names>F.</given-names></name><name><surname>Wang</surname><given-names>X.</given-names></name><name><surname>Bertolotti</surname><given-names>A.</given-names></name><name><surname>Zhang</surname><given-names>Y.</given-names></name><name><surname>Chung</surname><given-names>P.</given-names></name><name><surname>Harding</surname><given-names>H.P.</given-names></name><name><surname>Ron</surname><given-names>D.</given-names></name></person-group><article-title>Coupling of Stress in the ER to Activation of JNK Protein Kinases by Transmembrane Protein Kinase IRE1</article-title><source>Science</source><year>2000</year><volume>287</volume><fpage>664</fpage><lpage>666</lpage><pub-id pub-id-type="doi">10.1126/science.287.5453.664</pub-id><pub-id pub-id-type="pmid">10650002</pub-id></element-citation></ref><ref id="B172-diseases-04-00026"><label>172.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Versteeg</surname><given-names>G.A.</given-names></name><name><surname>van de Nes</surname><given-names>P.S.</given-names></name><name><surname>Bredenbeek</surname><given-names>P.J.</given-names></name><name><surname>Spaan</surname><given-names>W.J.M.</given-names></name></person-group><article-title>The Coronavirus Spike Protein Induces Endoplasmic Reticulum Stress and Upregulation of Intracellular Chemokine mRNA Concentrations</article-title><source>J. Virol.</source><year>2007</year><volume>81</volume><fpage>10981</fpage><lpage>10990</lpage><pub-id pub-id-type="doi">10.1128/JVI.01033-07</pub-id><pub-id pub-id-type="pmid">17670839</pub-id></element-citation></ref><ref id="B173-diseases-04-00026"><label>173.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fung</surname><given-names>T.S.</given-names></name><name><surname>Liao</surname><given-names>Y.</given-names></name><name><surname>Liu</surname><given-names>D.X.</given-names></name></person-group><article-title>The Endoplasmic Reticulum Stress Sensor IRE1α Protects Cells from Apoptosis Induced by the Coronavirus Infectious Bronchitis Virus</article-title><source>J. Virol.</source><year>2014</year><volume>88</volume><fpage>12752</fpage><lpage>12764</lpage><pub-id pub-id-type="doi">10.1128/JVI.02138-14</pub-id><pub-id pub-id-type="pmid">25142592</pub-id></element-citation></ref><ref id="B174-diseases-04-00026"><label>174.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dhillon</surname><given-names>A.S.</given-names></name><name><surname>Hagan</surname><given-names>S.</given-names></name><name><surname>Rath</surname><given-names>O.</given-names></name><name><surname>Kolch</surname><given-names>W.</given-names></name></person-group><article-title>MAP kinase signalling pathways in cancer</article-title><source>Oncogene</source><year>0000</year><volume>26</volume><fpage>3279</fpage><lpage>3290</lpage><pub-id pub-id-type="doi">10.1038/sj.onc.1210421</pub-id><pub-id pub-id-type="pmid">17496922</pub-id></element-citation></ref><ref id="B175-diseases-04-00026"><label>175.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Davis</surname><given-names>R.J.</given-names></name></person-group><article-title>Signal Transduction to the Nucleus by MAP Kinase</article-title><source>Signaling Networks and Cell Cycle Control: The Molecular Basis of Cancer and Other Diseases</source><person-group person-group-type="editor"><name><surname>Gutkind</surname><given-names>J.S.</given-names></name></person-group><publisher-name>Humana Press</publisher-name><publisher-loc>Totowa, NJ, USA</publisher-loc><year>2000</year><fpage>153</fpage><lpage>164</lpage></element-citation></ref><ref id="B176-diseases-04-00026"><label>176.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Panteva</surname><given-names>M.</given-names></name><name><surname>Korkaya</surname><given-names>H.</given-names></name><name><surname>Jameel</surname><given-names>S.</given-names></name></person-group><article-title>Hepatitis viruses and the MAPK pathway: Is this a survival strategy?</article-title><source>Virus Res.</source><year>2003</year><volume>92</volume><fpage>131</fpage><lpage>140</lpage><pub-id pub-id-type="doi">10.1016/S0168-1702(02)00356-8</pub-id><pub-id pub-id-type="pmid">12686421</pub-id></element-citation></ref><ref id="B177-diseases-04-00026"><label>177.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arthur</surname><given-names>J.S.C.</given-names></name><name><surname>Ley</surname><given-names>S.C.</given-names></name></person-group><article-title>Mitogen-activated protein kinases in innate immunity</article-title><source>Nat. Rev. Immunol.</source><year>2013</year><volume>13</volume><fpage>679</fpage><lpage>692</lpage><pub-id pub-id-type="doi">10.1038/nri3495</pub-id><pub-id pub-id-type="pmid">23954936</pub-id></element-citation></ref><ref id="B178-diseases-04-00026"><label>178.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Keshet</surname><given-names>Y.</given-names></name><name><surname>Seger</surname><given-names>R.</given-names></name></person-group><article-title>The MAP Kinase Signaling Cascades: A System of Hundreds of Components Regulates a Diverse Array of Physiological Functions</article-title><source>MAP Kinase Signaling Protocols</source><edition>2nd ed.</edition><person-group person-group-type="editor"><name><surname>Peger</surname><given-names>R.</given-names></name></person-group><publisher-name>Humana Press</publisher-name><publisher-loc>Totowa, NJ, USA</publisher-loc><year>2010</year><fpage>3</fpage><lpage>38</lpage></element-citation></ref><ref id="B179-diseases-04-00026"><label>179.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mizutani</surname><given-names>T.</given-names></name><name><surname>Fukushi</surname><given-names>S.</given-names></name><name><surname>Murakami</surname><given-names>M.</given-names></name><name><surname>Hirano</surname><given-names>T.</given-names></name><name><surname>Saijo</surname><given-names>M.</given-names></name><name><surname>Kurane</surname><given-names>I.</given-names></name><name><surname>Morikawa</surname><given-names>S.</given-names></name></person-group><article-title>Tyrosine dephosphorylation of STAT3 in SARS coronavirus-infected Vero E6 cells</article-title><source>FEBS Lett.</source><year>2004</year><volume>577</volume><fpage>187</fpage><lpage>192</lpage><pub-id pub-id-type="doi">10.1016/j.febslet.2004.10.005</pub-id><pub-id pub-id-type="pmid">15527783</pub-id></element-citation></ref><ref id="B180-diseases-04-00026"><label>180.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mizutani</surname><given-names>T.</given-names></name><name><surname>Fukushi</surname><given-names>S.</given-names></name><name><surname>Saijo</surname><given-names>M.</given-names></name><name><surname>Kurane</surname><given-names>I.</given-names></name><name><surname>Morikawa</surname><given-names>S.</given-names></name></person-group><article-title>Phosphorylation of p38 MAPK and its downstream targets in SARS coronavirus-infected cells</article-title><source>Biochem. Biophys. Res. Commun.</source><year>2004</year><volume>319</volume><fpage>1228</fpage><lpage>1234</lpage><pub-id pub-id-type="doi">10.1016/j.bbrc.2004.05.107</pub-id><pub-id pub-id-type="pmid">15194498</pub-id></element-citation></ref><ref id="B181-diseases-04-00026"><label>181.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>I.Y.</given-names></name><name><surname>Chang</surname><given-names>S.C.</given-names></name><name><surname>Wu</surname><given-names>H.-Y.</given-names></name><name><surname>Yu</surname><given-names>T.-C.</given-names></name><name><surname>Wei</surname><given-names>W.-C.</given-names></name><name><surname>Lin</surname><given-names>S.</given-names></name><name><surname>Chien</surname><given-names>C.L.</given-names></name><name><surname>Chang</surname><given-names>M.F.</given-names></name></person-group><article-title>Upregulation of the Chemokine (C-C Motif) Ligand 2 via a Severe Acute Respiratory Syndrome Coronavirus Spike-ACE2 Signaling Pathway</article-title><source>J. Virol.</source><year>2010</year><volume>84</volume><fpage>7703</fpage><lpage>7712</lpage><pub-id pub-id-type="doi">10.1128/JVI.02560-09</pub-id><pub-id pub-id-type="pmid">20484496</pub-id></element-citation></ref><ref id="B182-diseases-04-00026"><label>182.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mizutani</surname><given-names>T.</given-names></name><name><surname>Fukushi</surname><given-names>S.</given-names></name><name><surname>Saijo</surname><given-names>M.</given-names></name><name><surname>Kurane</surname><given-names>I.</given-names></name><name><surname>Morikawa</surname><given-names>S.</given-names></name></person-group><article-title>Regulation of p90RSK phosphorylation by SARS-CoV infection in Vero E6 cells</article-title><source>FEBS Lett.</source><year>2006</year><volume>580</volume><fpage>1417</fpage><lpage>1424</lpage><pub-id pub-id-type="doi">10.1016/j.febslet.2006.01.066</pub-id><pub-id pub-id-type="pmid">16458888</pub-id></element-citation></ref><ref id="B183-diseases-04-00026"><label>183.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yao</surname><given-names>Y.</given-names></name><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Wu</surname><given-names>J.</given-names></name><name><surname>Germann</surname><given-names>U.A.</given-names></name><name><surname>Su</surname><given-names>M.S.</given-names></name><name><surname>Kuida</surname><given-names>K.</given-names></name><name><surname>Boucher</surname><given-names>D.M.</given-names></name></person-group><article-title>Extracellular Signal-Regulated Kinase 2 Is Necessary for Mesoderm Differentiation</article-title><source>Proc. Natl. Acad. Sci. USA</source><year>2003</year><volume>100</volume><fpage>12759</fpage><lpage>12764</lpage><pub-id pub-id-type="doi">10.1073/pnas.2134254100</pub-id><pub-id pub-id-type="pmid">14566055</pub-id></element-citation></ref><ref id="B184-diseases-04-00026"><label>184.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yu</surname><given-names>Y.T.-C.</given-names></name><name><surname>Chien</surname><given-names>S.-C.</given-names></name><name><surname>Chen</surname><given-names>I.Y.</given-names></name><name><surname>Lai</surname><given-names>C.-T.</given-names></name><name><surname>Tsay</surname><given-names>Y.-G.</given-names></name><name><surname>Chang</surname><given-names>S.C.</given-names></name><name><surname>Chang</surname><given-names>M.F.</given-names></name></person-group><article-title>Surface vimentin is critical for the cell entry of SARS-CoV</article-title><source>J. Biomed.Sci.</source><year>2016</year><volume>23</volume><fpage>14</fpage><pub-id pub-id-type="doi">10.1186/s12929-016-0234-7</pub-id><pub-id pub-id-type="pmid">26801988</pub-id></element-citation></ref><ref id="B185-diseases-04-00026"><label>185.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kumar</surname><given-names>N.</given-names></name><name><surname>Robidoux</surname><given-names>J.</given-names></name><name><surname>Daniel</surname><given-names>K.W.</given-names></name><name><surname>Guzman</surname><given-names>G.</given-names></name><name><surname>Floering</surname><given-names>L.M.</given-names></name><name><surname>Collins</surname><given-names>S.</given-names></name></person-group><article-title>Requirement of Vimentin Filament Assembly for β3-Adrenergic Receptor Activation of ERK MAP Kinase and Lipolysis</article-title><source>J. Biol. Chem.</source><year>2007</year><volume>282</volume><fpage>9244</fpage><lpage>9250</lpage><pub-id pub-id-type="doi">10.1074/jbc.M605571200</pub-id><pub-id pub-id-type="pmid">17251187</pub-id></element-citation></ref><ref id="B186-diseases-04-00026"><label>186.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chang</surname><given-names>Y.-J.</given-names></name><name><surname>Liu</surname><given-names>C.Y.-Y.</given-names></name><name><surname>Chiang</surname><given-names>B.-L.</given-names></name><name><surname>Chao</surname><given-names>Y.-C.</given-names></name><name><surname>Chen</surname><given-names>C.-C.</given-names></name></person-group><article-title>Induction of IL-8 Release in Lung Cells via Activator Protein-1 by Recombinant Baculovirus Displaying Severe Acute Respiratory Syndrome-Coronavirus Spike Proteins: Identification of Two Functional Regions</article-title><source>J. Immunol.</source><year>2004</year><volume>173</volume><fpage>7602</fpage><lpage>7614</lpage><pub-id pub-id-type="doi">10.4049/jimmunol.173.12.7602</pub-id><pub-id pub-id-type="pmid">15585888</pub-id></element-citation></ref><ref id="B187-diseases-04-00026"><label>187.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>S.-W.</given-names></name><name><surname>Lai</surname><given-names>C.-C.</given-names></name><name><surname>Ping</surname><given-names>J.-F.</given-names></name><name><surname>Tsai</surname><given-names>F.-J.</given-names></name><name><surname>Wan</surname><given-names>L.</given-names></name><name><surname>Lin</surname><given-names>Y.-J.</given-names></name><name><surname>Kung</surname><given-names>S.H.</given-names></name><name><surname>Lin</surname><given-names>C.W.</given-names></name></person-group><article-title>Severe acute respiratory syndrome coronavirus papain-like protease suppressed alpha interferon-induced responses through downregulation of extracellular signal-regulated kinase 1-mediated signalling pathways</article-title><source>J. Gen. Virol.</source><year>2011</year><volume>92</volume><fpage>1127</fpage><lpage>1140</lpage><pub-id pub-id-type="doi">10.1099/vir.0.028936-0</pub-id><pub-id pub-id-type="pmid">21270289</pub-id></element-citation></ref><ref id="B188-diseases-04-00026"><label>188.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Varshney</surname><given-names>B.</given-names></name><name><surname>Lal</surname><given-names>S.</given-names></name></person-group><article-title>SARS-CoV Accessory Protein 3b Induces AP-1 Transcriptional Activity through Activation of JNK and ERK Pathways</article-title><source>Biochemistry</source><year>2011</year><volume>50</volume><fpage>5419</fpage><lpage>5425</lpage><pub-id pub-id-type="doi">10.1021/bi200303r</pub-id><pub-id pub-id-type="pmid">21561061</pub-id></element-citation></ref><ref id="B189-diseases-04-00026"><label>189.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kindrachuk</surname><given-names>J.</given-names></name><name><surname>Ork</surname><given-names>B.</given-names></name><name><surname>Hart</surname><given-names>B.J.</given-names></name><name><surname>Mazur</surname><given-names>S.</given-names></name><name><surname>Holbrook</surname><given-names>M.R.</given-names></name><name><surname>Frieman</surname><given-names>M.B.</given-names></name><name><surname>Traynor</surname><given-names>D.</given-names></name><name><surname>Johnson</surname><given-names>R.F.</given-names></name><name><surname>Dyall</surname><given-names>J.</given-names></name><name><surname>Kuhn</surname><given-names>J.H.</given-names></name><etal></etal></person-group><article-title>Antiviral Potential of ERK/MAPK and PI3K/AKT/mTOR Signaling Modulation for Middle East Respiratory Syndrome Coronavirus Infection as Identified by Temporal Kinome Analysis</article-title><source>Antimicrob. Agents Chemother.</source><year>2015</year><volume>59</volume><fpage>1088</fpage><lpage>1099</lpage><pub-id pub-id-type="doi">10.1128/AAC.03659-14</pub-id><pub-id pub-id-type="pmid">25487801</pub-id></element-citation></ref><ref id="B190-diseases-04-00026"><label>190.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kono</surname><given-names>M.</given-names></name><name><surname>Tatsumi</surname><given-names>K.</given-names></name><name><surname>Imai</surname><given-names>A.M.</given-names></name><name><surname>Saito</surname><given-names>K.</given-names></name><name><surname>Kuriyama</surname><given-names>T.</given-names></name><name><surname>Shirasawa</surname><given-names>H.</given-names></name></person-group><article-title>Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK</article-title><source>Antivir. Res.</source><year>2008</year><volume>77</volume><fpage>150</fpage><lpage>152</lpage><pub-id pub-id-type="doi">10.1016/j.antiviral.2007.10.011</pub-id><pub-id pub-id-type="pmid">18055026</pub-id></element-citation></ref><ref id="B191-diseases-04-00026"><label>191.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mizutani</surname><given-names>T.</given-names></name><name><surname>Fukushi</surname><given-names>S.</given-names></name><name><surname>Saijo</surname><given-names>M.</given-names></name><name><surname>Kurane</surname><given-names>I.</given-names></name><name><surname>Morikawa</surname><given-names>S.</given-names></name></person-group><article-title>JNK and PI3k/Akt signaling pathways are required for establishing persistent SARS-CoV infection in Vero E6 cells</article-title><source>Biochim. Biophys. Acta</source><year>2005</year><volume>1741</volume><fpage>4</fpage><lpage>10</lpage><pub-id pub-id-type="doi">10.1016/j.bbadis.2005.04.004</pub-id><pub-id pub-id-type="pmid">15916886</pub-id></element-citation></ref><ref id="B192-diseases-04-00026"><label>192.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kanzawa</surname><given-names>N.</given-names></name><name><surname>Nishigaki</surname><given-names>K.</given-names></name><name><surname>Hayashi</surname><given-names>T.</given-names></name><name><surname>Ishii</surname><given-names>Y.</given-names></name><name><surname>Furukawa</surname><given-names>S.</given-names></name><name><surname>Niiro</surname><given-names>A.</given-names></name><name><surname>Yasui</surname><given-names>F.</given-names></name><name><surname>Kohara</surname><given-names>M.</given-names></name><name><surname>Morita</surname><given-names>K.</given-names></name><name><surname>Matsushima</surname><given-names>K.</given-names></name><etal></etal></person-group><article-title>Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-κB activation</article-title><source>FEBS Lett.</source><year>2006</year><volume>580</volume><fpage>6807</fpage><lpage>6812</lpage><pub-id pub-id-type="doi">10.1016/j.febslet.2006.11.046</pub-id><pub-id pub-id-type="pmid">17141229</pub-id></element-citation></ref><ref id="B193-diseases-04-00026"><label>193.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>M.</given-names></name><name><surname>Yang</surname><given-names>Y.</given-names></name><name><surname>Gu</surname><given-names>C.</given-names></name><name><surname>Yue</surname><given-names>Y.</given-names></name><name><surname>Wu</surname><given-names>K.K.</given-names></name><name><surname>Wu</surname><given-names>J.</given-names></name><name><surname>Zhu</surname><given-names>Y.</given-names></name></person-group><article-title>Spike protein of SARS-CoV stimulates cyclooxygenase-2 expression via both calcium-dependent and calcium-independent protein kinase C pathways</article-title><source>FASEB J.</source><year>2007</year><volume>21</volume><fpage>1586</fpage><lpage>1596</lpage><pub-id pub-id-type="doi">10.1096/fj.06-6589com</pub-id><pub-id pub-id-type="pmid">17267381</pub-id></element-citation></ref><ref id="B194-diseases-04-00026"><label>194.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Fung</surname><given-names>T.S.</given-names></name></person-group><article-title>Molecular Characterization of Cellular Stress Responses during Coronavirus Infection</article-title><source>Ph.D. Thesis</source><publisher-name>Nanyang Technological University</publisher-name><publisher-loc>Singapore, Singapore</publisher-loc><year>2015</year></element-citation></ref><ref id="B195-diseases-04-00026"><label>195.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kopecky-Bromberg</surname><given-names>S.A.</given-names></name><name><surname>Martinez-Sobrido</surname><given-names>L.</given-names></name><name><surname>Palese</surname><given-names>P.</given-names></name></person-group><article-title>7a Protein of Severe Acute Respiratory Syndrome Coronavirus Inhibits Cellular Protein Synthesis and Activates p38 Mitogen-Activated Protein Kinase</article-title><source>J. Virol.</source><year>2006</year><volume>80</volume><fpage>785</fpage><lpage>793</lpage><pub-id pub-id-type="doi">10.1128/JVI.80.2.785-793.2006</pub-id><pub-id pub-id-type="pmid">16378980</pub-id></element-citation></ref><ref id="B196-diseases-04-00026"><label>196.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tan</surname><given-names>Y.-J.</given-names></name><name><surname>Teng</surname><given-names>E.</given-names></name><name><surname>Shen</surname><given-names>S.</given-names></name><name><surname>Tan</surname><given-names>T.H.P.</given-names></name><name><surname>Goh</surname><given-names>P.-Y.</given-names></name><name><surname>Fielding</surname><given-names>B.C.</given-names></name><name><surname>Ooi</surname><given-names>E.E.</given-names></name><name><surname>Tan</surname><given-names>H.C.</given-names></name><name><surname>Lim</surname><given-names>S.G.</given-names></name><name><surname>Hong</surname><given-names>W.</given-names></name></person-group><article-title>A Novel Severe Acute Respiratory Syndrome Coronavirus Protein, U274, Is Transported to the Cell Surface and Undergoes Endocytosis</article-title><source>J. Virol.</source><year>2004</year><volume>78</volume><fpage>6723</fpage><lpage>6734</lpage><pub-id pub-id-type="doi">10.1128/JVI.78.13.6723-6734.2004</pub-id><pub-id pub-id-type="pmid">15194747</pub-id></element-citation></ref><ref id="B197-diseases-04-00026"><label>197.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jimenez-Guardeño</surname><given-names>J.M.</given-names></name><name><surname>Nieto-Torres</surname><given-names>J.L.</given-names></name><name><surname>DeDiego</surname><given-names>M.L.</given-names></name><name><surname>Regla-Nava</surname><given-names>J.A.</given-names></name><name><surname>Fernandez-Delgado</surname><given-names>R.</given-names></name><name><surname>Castaño-Rodriguez</surname><given-names>C.</given-names></name><name><surname>Enjuanes</surname><given-names>L.</given-names></name></person-group><article-title>The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis</article-title><source>PLoS Pathog.</source><year>2014</year><volume>10</volume><elocation-id>e1004320</elocation-id><pub-id pub-id-type="doi">10.1371/journal.ppat.1004320</pub-id><pub-id pub-id-type="pmid">25122212</pub-id></element-citation></ref><ref id="B198-diseases-04-00026"><label>198.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>C.-H.</given-names></name><name><surname>Chen</surname><given-names>R.-F.</given-names></name><name><surname>Liu</surname><given-names>J.-W.</given-names></name><name><surname>Yeh</surname><given-names>W.-T.</given-names></name><name><surname>Chang</surname><given-names>J.-C.</given-names></name><name><surname>Liu</surname><given-names>P.-M.</given-names></name><name><surname>Eng</surname><given-names>H.L.</given-names></name><name><surname>Lin</surname><given-names>M.C.</given-names></name><name><surname>Yang</surname><given-names>K.D.</given-names></name></person-group><article-title>Altered p38 Mitogen-Activated Protein Kinase Expression in Different Leukocytes with Increment of Immunosuppressive Mediators in Patients with Severe Acute Respiratory Syndrome</article-title><source>J. Immunol.</source><year>2004</year><volume>172</volume><fpage>7841</fpage><lpage>7847</lpage><pub-id pub-id-type="doi">10.4049/jimmunol.172.12.7841</pub-id><pub-id pub-id-type="pmid">15187168</pub-id></element-citation></ref><ref id="B199-diseases-04-00026"><label>199.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Santoro</surname><given-names>M.</given-names></name><name><surname>Rossi</surname><given-names>A.</given-names></name><name><surname>Amici</surname><given-names>C.</given-names></name></person-group><article-title>NEW EMBO MEMBER’S REVIEW: NF-κB and virus infection: Who controls whom</article-title><source>EMBO J.</source><year>2003</year><volume>22</volume><fpage>2552</fpage><lpage>2560</lpage><pub-id pub-id-type="doi">10.1093/emboj/cdg267</pub-id><pub-id pub-id-type="pmid">12773372</pub-id></element-citation></ref><ref id="B200-diseases-04-00026"><label>200.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hoesel</surname><given-names>B.</given-names></name><name><surname>Schmid</surname><given-names>J.A.</given-names></name></person-group><article-title>The complexity of NF-κB signaling in inflammation and cancer</article-title><source>Mol. Cancer</source><year>2013</year><volume>12</volume><fpage>1</fpage><lpage>15</lpage><pub-id pub-id-type="doi">10.1186/1476-4598-12-86</pub-id><pub-id pub-id-type="pmid">23286373</pub-id></element-citation></ref><ref id="B201-diseases-04-00026"><label>201.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hiscott</surname><given-names>J.</given-names></name><name><surname>Kwon</surname><given-names>H.</given-names></name><name><surname>Génin</surname><given-names>P.</given-names></name></person-group><article-title>Hostile takeovers: Viral appropriation of the NF-κB pathway</article-title><source>J. Clin. Investig.</source><year>2001</year><volume>107</volume><fpage>143</fpage><lpage>151</lpage><pub-id pub-id-type="doi">10.1172/JCI11918</pub-id><pub-id pub-id-type="pmid">11160127</pub-id></element-citation></ref><ref id="B202-diseases-04-00026"><label>202.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sun</surname><given-names>S.-C.</given-names></name></person-group><article-title>Non-canonical NF-κB signaling pathway</article-title><source>Cell Res.</source><year>2011</year><volume>21</volume><fpage>71</fpage><lpage>85</lpage><pub-id pub-id-type="doi">10.1038/cr.2010.177</pub-id><pub-id pub-id-type="pmid">21173796</pub-id></element-citation></ref><ref id="B203-diseases-04-00026"><label>203.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>De Diego</surname><given-names>M.L.</given-names></name><name><surname>Nieto-Torres</surname><given-names>J.L.</given-names></name><name><surname>Regla-Nava</surname><given-names>J.A.</given-names></name><name><surname>Jimenez-Guardeño</surname><given-names>J.M.</given-names></name><name><surname>Fernandez-Delgado</surname><given-names>R.</given-names></name><name><surname>Fett</surname><given-names>C.</given-names></name><name><surname>Castaño-Rodriguez</surname><given-names>C.</given-names></name><name><surname>Perlman</surname><given-names>S.</given-names></name><name><surname>Enjuanes</surname><given-names>L.</given-names></name></person-group><article-title>Inhibition of NF-κB-Mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival</article-title><source>J. Virol.</source><year>2014</year><volume>88</volume><fpage>913</fpage><lpage>924</lpage><pub-id pub-id-type="doi">10.1128/JVI.02576-13</pub-id><pub-id pub-id-type="pmid">24198408</pub-id></element-citation></ref><ref id="B204-diseases-04-00026"><label>204.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dosch</surname><given-names>S.F.</given-names></name><name><surname>Mahajan</surname><given-names>S.D.</given-names></name><name><surname>Collins</surname><given-names>A.R.</given-names></name></person-group><article-title>SARS Coronavirus Spike Protein-Induced Innate Immune Response occurs via Activation of the NF-κB pathway in Human Monocyte Macrophages in vitro</article-title><source>Virus Res.</source><year>2009</year><volume>142</volume><fpage>19</fpage><lpage>27</lpage><pub-id pub-id-type="doi">10.1016/j.virusres.2009.01.005</pub-id><pub-id pub-id-type="pmid">19185596</pub-id></element-citation></ref><ref id="B205-diseases-04-00026"><label>205.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liao</surname><given-names>Q.-J.</given-names></name><name><surname>Ye</surname><given-names>L.-B.</given-names></name><name><surname>Timani</surname><given-names>K.A.</given-names></name><name><surname>Zeng</surname><given-names>Y.-C.</given-names></name><name><surname>She</surname><given-names>Y.-L.</given-names></name><name><surname>Ye</surname><given-names>L.</given-names></name><name><surname>Wu</surname><given-names>Z.H.</given-names></name></person-group><article-title>Activation of NF-κB by the Full-length Nucleocapsid Protein of the SARS Coronavirus</article-title><source>Acta Biochim. Biophys. Sin.</source><year>2005</year><volume>37</volume><fpage>607</fpage><lpage>612</lpage><pub-id pub-id-type="doi">10.1111/j.1745-7270.2005.00082.x</pub-id><pub-id pub-id-type="pmid">16143815</pub-id></element-citation></ref><ref id="B206-diseases-04-00026"><label>206.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>He</surname><given-names>R.</given-names></name><name><surname>Leeson</surname><given-names>A.</given-names></name><name><surname>Andonov</surname><given-names>A.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Bastien</surname><given-names>N.</given-names></name><name><surname>Cao</surname><given-names>J.</given-names></name><name><surname>Osiowy</surname><given-names>C.</given-names></name><name><surname>Dobie</surname><given-names>F.</given-names></name><name><surname>Cutts</surname><given-names>T.</given-names></name><name><surname>Ballantine</surname><given-names>M.</given-names></name><etal></etal></person-group><article-title>Activation of AP-1 signal transduction pathway by SARS coronavirus nucleocapsid protein</article-title><source>Biochem. Biophys. Res. Commun.</source><year>2003</year><volume>311</volume><fpage>870</fpage><lpage>876</lpage><pub-id pub-id-type="doi">10.1016/j.bbrc.2003.10.075</pub-id><pub-id pub-id-type="pmid">14623261</pub-id></element-citation></ref><ref id="B207-diseases-04-00026"><label>207.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fang</surname><given-names>X.</given-names></name><name><surname>Gao</surname><given-names>J.</given-names></name><name><surname>Zheng</surname><given-names>H.</given-names></name><name><surname>Li</surname><given-names>B.</given-names></name><name><surname>Kong</surname><given-names>L.</given-names></name><name><surname>Zhang</surname><given-names>Y.</given-names></name><name><surname>Wang</surname><given-names>W.</given-names></name><name><surname>Zeng</surname><given-names>Y.</given-names></name><name><surname>Ye</surname><given-names>L.</given-names></name></person-group><article-title>The membrane protein of SARS-CoV suppresses NF-κB activation</article-title><source>J. Med. Virol.</source><year>2007</year><volume>79</volume><fpage>1431</fpage><lpage>1439</lpage><pub-id pub-id-type="doi">10.1002/jmv.20953</pub-id><pub-id pub-id-type="pmid">17705188</pub-id></element-citation></ref><ref id="B208-diseases-04-00026"><label>208.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lai</surname><given-names>F.W.</given-names></name><name><surname>Stephenson</surname><given-names>K.B.</given-names></name><name><surname>Mahony</surname><given-names>J.</given-names></name><name><surname>Lichty</surname><given-names>B.D.</given-names></name></person-group><article-title>Human Coronavirus OC43 Nucleocapsid Protein Binds MicroRNA 9 and Potentiates NF-κB Activation</article-title><source>J. Virol.</source><year>2014</year><volume>88</volume><fpage>54</fpage><lpage>65</lpage><pub-id pub-id-type="doi">10.1128/JVI.02678-13</pub-id><pub-id pub-id-type="pmid">24109243</pub-id></element-citation></ref><ref id="B209-diseases-04-00026"><label>209.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Law</surname><given-names>A.H.Y.</given-names></name><name><surname>Lee</surname><given-names>D.C.W.</given-names></name><name><surname>Cheung</surname><given-names>B.K.W.</given-names></name><name><surname>Yim</surname><given-names>H.C.H.</given-names></name><name><surname>Lau</surname><given-names>A.S.Y.</given-names></name></person-group><article-title>Role for Nonstructural Protein 1 of Severe Acute Respiratory Syndrome Coronavirus in Chemokine Dysregulation</article-title><source>J. Virol.</source><year>2007</year><volume>81</volume><fpage>416</fpage><lpage>422</lpage><pub-id pub-id-type="doi">10.1128/JVI.02336-05</pub-id><pub-id pub-id-type="pmid">17035307</pub-id></element-citation></ref><ref id="B210-diseases-04-00026"><label>210.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Frieman</surname><given-names>M.</given-names></name><name><surname>Ratia</surname><given-names>K.</given-names></name><name><surname>Johnston</surname><given-names>R.E.</given-names></name><name><surname>Mesecar</surname><given-names>A.D.</given-names></name><name><surname>Baric</surname><given-names>R.S.</given-names></name></person-group><article-title>Severe Acute Respiratory Syndrome Coronavirus Papain-Like Protease Ubiquitin-Like Domain and Catalytic Domain Regulate Antagonism of IRF3 and NF-κB Signaling</article-title><source>J. Virol.</source><year>2009</year><volume>83</volume><fpage>6689</fpage><lpage>6705</lpage><pub-id pub-id-type="doi">10.1128/JVI.02220-08</pub-id><pub-id pub-id-type="pmid">19369340</pub-id></element-citation></ref><ref id="B211-diseases-04-00026"><label>211.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ratia</surname><given-names>K.</given-names></name><name><surname>Kilianski</surname><given-names>A.</given-names></name><name><surname>Baez-Santos</surname><given-names>Y.M.</given-names></name><name><surname>Baker</surname><given-names>S.C.</given-names></name><name><surname>Mesecar</surname><given-names>A.</given-names></name></person-group><article-title>Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating Activity of SARS-CoV Papain-Like Protease</article-title><source>PLoS Pathog.</source><year>2014</year><volume>10</volume><elocation-id>e1004113</elocation-id><pub-id pub-id-type="doi">10.1371/journal.ppat.1004113</pub-id><pub-id pub-id-type="pmid">24854014</pub-id></element-citation></ref><ref id="B212-diseases-04-00026"><label>212.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Matthews</surname><given-names>K.L.</given-names></name><name><surname>Coleman</surname><given-names>C.M.</given-names></name><name><surname>van der Meer</surname><given-names>Y.</given-names></name><name><surname>Snijder</surname><given-names>E.J.</given-names></name><name><surname>Frieman</surname><given-names>M.B.</given-names></name></person-group><article-title>The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling</article-title><source>J. Gen. Virol.</source><year>2014</year><volume>95</volume><fpage>874</fpage><lpage>882</lpage><pub-id pub-id-type="doi">10.1099/vir.0.062059-0</pub-id><pub-id pub-id-type="pmid">24443473</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="diseases-04-00026-f001" position="float"><label>Figure 1</label><caption><p>Genome organisation of human coronaviruses (HCoVs). HCoV genomes range from about 26 to 32 kilobases (kb) in size, as indicated by the black lines above the scale. Coronavirus (CoV) genome is typically arranged in the order of 5′-ORF1a-ORF1b-S-E-M-N-3′. The overlapping open reading frames (ORF) ORF1a and ORF1b comprise two-thirds of the coronavirus genome, which encodes for all the viral components required for viral RNA synthesis. The other one-third of the genome at the 3′ end encodes for a set of structural (<bold>orange</bold>) and non-structural proteins (<bold>green</bold>).</p></caption><graphic xlink:href="diseases-04-00026-g001"></graphic></fig><fig id="diseases-04-00026-f002" position="float"><label>Figure 2</label><caption><p>Coronavirus replication cycle. Coronavirus infection begins with the attachment of the S1 domain of the spike protein (S) with its cognate receptor. This drives the conformational change in the S2 subunit in S, promoting the fusion of the viral and cell plasma membrane. Following the release of the nucleocapsid to the cytoplasm, the viral gRNA is translated through ribosomal frameshifting to produce polyproteins pp1a and pp1ab. pp1a and pp1ab are autoproteolytically processed by host and viral proteases to generate 16 non-structural proteins (NSPs), which will then be assembled to form the replicase-polymerase. The replicase-polymerase is involved in the coronaviral replication, a process in which the genomic RNA are replicated and the subgenomic RNA will be transcribed and translated to form the structural proteins. The viral products produced will be assembled in the ERGIC, and bud out as a smooth-wall vesicle to the plasma membrane to egress via exocytosis. Host factors that promote infection and inhibit infection are highlighted in green and red, respectively. APN, aminopeptidase N; ACE2, Angiotensin converting enzyme 2; DPP4, dipeptidyl peptidase 4; 9-<italic>O</italic>-Ac Sialic Acid, 9-<italic>O</italic>-Acetylated Sialic Acid; IFITM, Interferon induced transmembrane protein; ATP1A1, ATPase, Na<sup>+</sup>/K<sup>+</sup> Transporting, Alpha 1 Polypeptide; HnRNP A1, Heterogeneous nuclear ribonucleoprotein A1; MADP1, Zinc Finger CCHC-Type and RNA Binding Motif 1; DDX1, ATP-dependent RNA Helicase; PCBP1/2, Poly r(C) binding protein 1/2; PABP, Poly A binding protein; COPB2, Coatomer protein complex, subunit beta 2 (beta prime); GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; ERGIC, Endoplasmic reticulum Golgi intermediate compartment; ER, endoplasmic reticulum; VCP, Valosin-Containing Protein.</p></caption><graphic xlink:href="diseases-04-00026-g002"></graphic></fig><fig id="diseases-04-00026-f003" position="float"><label>Figure 3</label><caption><p>Regulation of MOMP by Bcl2 family of proteins. (<bold>a</bold>) The Bcl2 family of proteins is categorized into three main classes according to their functions and number of Bcl2 homology (BH) domains. The pro-survival Bcl2-like family members (Bcl2, B-cell lymphoma-extra-large (Bcl-XL), myeloid cell leukemia (Mcl1)) contain all four BH domains and are anti-apoptotic. A second class, known as Bcl2-associated X (BAX)-like proteins, which includes BAX and Bcl2 homologous antagonist killer (BAK), is pro-apoptotic and lacks the BH4 domain. Finally, the third class, known as BH3-only proteins (Bid, Bcl2-associated death promoter (Bad), and p53-upregulated modulator of apoptosis (PUMA)), contain only BH3 domain and is pro-apoptotic. (<bold>b</bold>) Two models have been proposed to account for the role of the Bcl2 family proteins in MOMP—the indirect activator model and direct activator–depressor model [<xref rid="B11-diseases-04-00026" ref-type="bibr">11</xref>]. In the indirect activator model, the anti-apoptotic Bcl2-like proteins suppress the insertion of Bax-Bak pore complex into the mitochondria to promote MOMP and release of cytochrome c. However, when BH3-only proteins are activated beyond a certain threshold, the inhibitory effects of Bcl2-like proteins can be subverted. In the direct activator–depressor model, BH3-only protein acts as direct activators to induce Bak-Bak insertion into the outer mitochondrial membrane. These BH3-only proteins can be suppressed by Bcl2-like protein, which can in turn be inhibited by another subset of BH3-only proteins. This figure is modified from [<xref rid="B12-diseases-04-00026" ref-type="bibr">12</xref>].</p></caption><graphic xlink:href="diseases-04-00026-g003"></graphic></fig><fig id="diseases-04-00026-f004" position="float"><label>Figure 4</label><caption><p>Activation of apoptosis by HCoVs. Binding of death ligands to death receptor induces caspase 8 activation, which in turn activates effector caspases 3 and 7 to stimulate apoptosis. On the other hand, intrinsic pathway is regulated by pro-apoptotic and anti-apoptotic Bcl2 family proteins, such as Bcl-XL, Bcl2, Bax and Bak to induce MOMP. Subsequent caspase 9 activation caused by enhanced MOMP stimulates caspases 3 and 7 activation. During HCoV infection, the virus or specific viral proteins (yellow-orange boxes) target at multiple stages of both the extrinsic and intrinsic apoptosis signalling pathways.</p></caption><graphic xlink:href="diseases-04-00026-g004"></graphic></fig><fig id="diseases-04-00026-f005" position="float"><label>Figure 5</label><caption><p>HCoV viral proteins on innate immunity. During HCoV infection, PRRs such as TLRs, RIG-I and MDA5 are activated to trigger a series of signalling pathway, including MAPK and NF-κB, for IFN production. These IFNs then act on IFNAR and activate the JAK-STAT signalling pathway to induce ISGs. The yellow-orange boxes show the viral proteins that have been reported to modulate host innate immunity at multiple stages.</p></caption><graphic xlink:href="diseases-04-00026-g005"></graphic></fig><fig id="diseases-04-00026-f006" position="float"><label>Figure 6</label><caption><p>HCoVs on ER stress response. During HCoV infections, the ER stress response, which comprises of three signalling pathways, PERK, ATF6 and IRE1, is activated. HCoVs encode many viral proteins (yellow-orange boxes) that target the various signalling pathway of ER stress during viral infections.</p></caption><graphic xlink:href="diseases-04-00026-g006"></graphic></fig><fig id="diseases-04-00026-f007" position="float"><label>Figure 7</label><caption><p>HCoVs on MAPK signalling pathways. MAPK pathways comprises of the ERK, JNK and p38 MAPK pathways. During HCoV infections, the signals are transduced by the MAPK pathways by a three-tier protein kinase cascade, with the kinase of each tier being phosphorylated by upstream kinases at the Thr and Tyr residues. HCoVs and their viral proteins (yellow-orange boxes) have been shown to induce these MAPK pathways as shown in the figure.</p></caption><graphic xlink:href="diseases-04-00026-g007"></graphic></fig><table-wrap id="diseases-04-00026-t001" position="float"><object-id pub-id-type="pii">diseases-04-00026-t001_Table 1</object-id><label>Table 1</label><caption><p>Classification of human coronavirus.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Coronaviriniae Genera</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Strains</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Discovery</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Cellular Receptor</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Host</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1"><bold>Alpha-coronavirus</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">HCoV-229E</td><td align="center" valign="middle" rowspan="1" colspan="1">1966</td><td align="center" valign="middle" rowspan="1" colspan="1">Human Aminopeptidase N (CD13)</td><td align="center" valign="middle" rowspan="1" colspan="1">Bats</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B1-diseases-04-00026" ref-type="bibr">1</xref>,<xref rid="B2-diseases-04-00026" ref-type="bibr">2</xref>,<xref rid="B21-diseases-04-00026" ref-type="bibr">21</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">HCoV-NL63</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2004</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ACE2</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Palm Civets, Bats</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B3-diseases-04-00026" ref-type="bibr">3</xref>,<xref rid="B21-diseases-04-00026" ref-type="bibr">21</xref>]</td></tr><tr><td rowspan="4" align="center" valign="middle" style="border-bottom:solid thin" colspan="1"><bold>Beta-coronavirus</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">HCoV-OC43</td><td align="center" valign="middle" rowspan="1" colspan="1">1967</td><td align="center" valign="middle" rowspan="1" colspan="1">9-<italic>O</italic>-Acetylated sialic acid</td><td align="center" valign="middle" rowspan="1" colspan="1">Cattle</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B4-diseases-04-00026" ref-type="bibr">4</xref>,<xref rid="B5-diseases-04-00026" ref-type="bibr">5</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">HcoV-HKU1</td><td align="center" valign="middle" rowspan="1" colspan="1">2005</td><td align="center" valign="middle" rowspan="1" colspan="1">9-<italic>O</italic>-Acetylated sialic acid</td><td align="center" valign="middle" rowspan="1" colspan="1">Mice</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B6-diseases-04-00026" ref-type="bibr">6</xref>,<xref rid="B7-diseases-04-00026" ref-type="bibr">7</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">SARS-CoV</td><td align="center" valign="middle" rowspan="1" colspan="1">2003</td><td align="center" valign="middle" rowspan="1" colspan="1">ACE2</td><td align="center" valign="middle" rowspan="1" colspan="1">Palm Civets, Bats</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B8-diseases-04-00026" ref-type="bibr">8</xref>,<xref rid="B19-diseases-04-00026" ref-type="bibr">19</xref>,<xref rid="B21-diseases-04-00026" ref-type="bibr">21</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MERS-CoV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2012</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">DPP4</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bats, Camels</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B9-diseases-04-00026" ref-type="bibr">9</xref>]</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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