Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding
Identifieur interne : 000E31 ( Pmc/Corpus ); précédent : 000E30; suivant : 000E32Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding
Auteurs : Susanna K P. Lau ; Libiao Zhang ; Hayes K H. Luk ; Lifeng Xiong ; Xingwen Peng ; Kenneth S M. Li ; Xiangyang He ; Pyrear Su-Hui Zhao ; Rachel Y Y. Fan ; Antonio C P. Wong ; Syed Shakeel Ahmed ; Jian-Piao Cai ; Jasper F W. Chan ; Yinyan Sun ; Dongyan Jin ; Honglin Chen ; Terrence C K. Lau ; Raven K H. Kok ; Wenhui Li ; Kwok-Yung Yuen ; Patrick C Y. WooSource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2018.
Abstract
The discovery of Hp-BatCoV HKU25 bridges the evolutionary gap between MERS-CoV and existing bat viruses, and suggests that bat viruses may have evolved to generate MERS-CoV through modulation of the spike protein for binding to hDPP4.
Url:
DOI: 10.1093/infdis/jiy018
PubMed: 29346682
PubMed Central: 7107427
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PMC:7107427Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding</title><author><name sortKey="Lau, Susanna K P" sort="Lau, Susanna K P" uniqKey="Lau S" first="Susanna K P" last="Lau">Susanna K P. Lau</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Zhang, Libiao" sort="Zhang, Libiao" uniqKey="Zhang L" first="Libiao" last="Zhang">Libiao Zhang</name><affiliation><nlm:aff id="AF0005">Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, and Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong Province, China</nlm:aff></affiliation></author><author><name sortKey="Luk, Hayes K H" sort="Luk, Hayes K H" uniqKey="Luk H" first="Hayes K H" last="Luk">Hayes K H. Luk</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Xiong, Lifeng" sort="Xiong, Lifeng" uniqKey="Xiong L" first="Lifeng" last="Xiong">Lifeng Xiong</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Peng, Xingwen" sort="Peng, Xingwen" uniqKey="Peng X" first="Xingwen" last="Peng">Xingwen Peng</name><affiliation><nlm:aff id="AF0005">Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, and Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong Province, China</nlm:aff></affiliation></author><author><name sortKey="Li, Kenneth S M" sort="Li, Kenneth S M" uniqKey="Li K" first="Kenneth S M" last="Li">Kenneth S M. Li</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="He, Xiangyang" sort="He, Xiangyang" uniqKey="He X" first="Xiangyang" last="He">Xiangyang He</name><affiliation><nlm:aff id="AF0005">Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, and Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong Province, China</nlm:aff></affiliation></author><author><name sortKey="Zhao, Pyrear Su Hui" sort="Zhao, Pyrear Su Hui" uniqKey="Zhao P" first="Pyrear Su-Hui" last="Zhao">Pyrear Su-Hui Zhao</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Fan, Rachel Y Y" sort="Fan, Rachel Y Y" uniqKey="Fan R" first="Rachel Y Y" last="Fan">Rachel Y Y. Fan</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Wong, Antonio C P" sort="Wong, Antonio C P" uniqKey="Wong A" first="Antonio C P" last="Wong">Antonio C P. Wong</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Ahmed, Syed Shakeel" sort="Ahmed, Syed Shakeel" uniqKey="Ahmed S" first="Syed Shakeel" last="Ahmed">Syed Shakeel Ahmed</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Cai, Jian Piao" sort="Cai, Jian Piao" uniqKey="Cai J" first="Jian-Piao" last="Cai">Jian-Piao Cai</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Chan, Jasper F W" sort="Chan, Jasper F W" uniqKey="Chan J" first="Jasper F W" last="Chan">Jasper F W. Chan</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Sun, Yinyan" sort="Sun, Yinyan" uniqKey="Sun Y" first="Yinyan" last="Sun">Yinyan Sun</name><affiliation><nlm:aff id="AF0006">National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Jin, Dongyan" sort="Jin, Dongyan" uniqKey="Jin D" first="Dongyan" last="Jin">Dongyan Jin</name><affiliation><nlm:aff id="AF0007">School of Biomedical Sciences, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Lau, Terrence C K" sort="Lau, Terrence C K" uniqKey="Lau T" first="Terrence C K" last="Lau">Terrence C K. Lau</name><affiliation><nlm:aff id="AF0008">Department of Biomedical Sciences, City University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Kok, Raven K H" sort="Kok, Raven K H" uniqKey="Kok R" first="Raven K H" last="Kok">Raven K H. Kok</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Li, Wenhui" sort="Li, Wenhui" uniqKey="Li W" first="Wenhui" last="Li">Wenhui Li</name><affiliation><nlm:aff id="AF0006">National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Woo, Patrick C Y" sort="Woo, Patrick C Y" uniqKey="Woo P" first="Patrick C Y" last="Woo">Patrick C Y. Woo</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29346682</idno><idno type="pmc">7107427</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107427</idno><idno type="RBID">PMC:7107427</idno><idno type="doi">10.1093/infdis/jiy018</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000E31</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000E31</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding</title><author><name sortKey="Lau, Susanna K P" sort="Lau, Susanna K P" uniqKey="Lau S" first="Susanna K P" last="Lau">Susanna K P. Lau</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Zhang, Libiao" sort="Zhang, Libiao" uniqKey="Zhang L" first="Libiao" last="Zhang">Libiao Zhang</name><affiliation><nlm:aff id="AF0005">Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, and Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong Province, China</nlm:aff></affiliation></author><author><name sortKey="Luk, Hayes K H" sort="Luk, Hayes K H" uniqKey="Luk H" first="Hayes K H" last="Luk">Hayes K H. Luk</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Xiong, Lifeng" sort="Xiong, Lifeng" uniqKey="Xiong L" first="Lifeng" last="Xiong">Lifeng Xiong</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Peng, Xingwen" sort="Peng, Xingwen" uniqKey="Peng X" first="Xingwen" last="Peng">Xingwen Peng</name><affiliation><nlm:aff id="AF0005">Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, and Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong Province, China</nlm:aff></affiliation></author><author><name sortKey="Li, Kenneth S M" sort="Li, Kenneth S M" uniqKey="Li K" first="Kenneth S M" last="Li">Kenneth S M. Li</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="He, Xiangyang" sort="He, Xiangyang" uniqKey="He X" first="Xiangyang" last="He">Xiangyang He</name><affiliation><nlm:aff id="AF0005">Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, and Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong Province, China</nlm:aff></affiliation></author><author><name sortKey="Zhao, Pyrear Su Hui" sort="Zhao, Pyrear Su Hui" uniqKey="Zhao P" first="Pyrear Su-Hui" last="Zhao">Pyrear Su-Hui Zhao</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Fan, Rachel Y Y" sort="Fan, Rachel Y Y" uniqKey="Fan R" first="Rachel Y Y" last="Fan">Rachel Y Y. Fan</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Wong, Antonio C P" sort="Wong, Antonio C P" uniqKey="Wong A" first="Antonio C P" last="Wong">Antonio C P. Wong</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Ahmed, Syed Shakeel" sort="Ahmed, Syed Shakeel" uniqKey="Ahmed S" first="Syed Shakeel" last="Ahmed">Syed Shakeel Ahmed</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Cai, Jian Piao" sort="Cai, Jian Piao" uniqKey="Cai J" first="Jian-Piao" last="Cai">Jian-Piao Cai</name><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Chan, Jasper F W" sort="Chan, Jasper F W" uniqKey="Chan J" first="Jasper F W" last="Chan">Jasper F W. Chan</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Sun, Yinyan" sort="Sun, Yinyan" uniqKey="Sun Y" first="Yinyan" last="Sun">Yinyan Sun</name><affiliation><nlm:aff id="AF0006">National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Jin, Dongyan" sort="Jin, Dongyan" uniqKey="Jin D" first="Dongyan" last="Jin">Dongyan Jin</name><affiliation><nlm:aff id="AF0007">School of Biomedical Sciences, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Lau, Terrence C K" sort="Lau, Terrence C K" uniqKey="Lau T" first="Terrence C K" last="Lau">Terrence C K. Lau</name><affiliation><nlm:aff id="AF0008">Department of Biomedical Sciences, City University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Kok, Raven K H" sort="Kok, Raven K H" uniqKey="Kok R" first="Raven K H" last="Kok">Raven K H. Kok</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Li, Wenhui" sort="Li, Wenhui" uniqKey="Li W" first="Wenhui" last="Li">Wenhui Li</name><affiliation><nlm:aff id="AF0006">National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Woo, Patrick C Y" sort="Woo, Patrick C Y" uniqKey="Woo P" first="Patrick C Y" last="Woo">Patrick C Y. Woo</name><affiliation><nlm:aff id="AF0001">State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Department of Microbiology The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0003">Carol Yu Centre for Infection The University of Hong Kong, China</nlm:aff></affiliation><affiliation><nlm:aff id="AF0004">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The discovery of Hp-BatCoV HKU25 bridges the evolutionary gap between MERS-CoV and existing bat viruses, and suggests that bat viruses may have evolved to generate MERS-CoV through modulation of the spike protein for binding to hDPP4.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Groot, Rj" uniqKey="De Groot R">RJ de Groot</name></author><author><name sortKey="Baker, Sc" uniqKey="Baker S">SC Baker</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Mou, H" uniqKey="Mou H">H Mou</name></author><author><name sortKey="Smits, Sl" uniqKey="Smits S">SL Smits</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reusken, Cb" uniqKey="Reusken C">CB Reusken</name></author><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Müller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Al Dhahiry, Sh" uniqKey="Al Dhahiry S">SH Al Dhahiry</name></author><author><name sortKey="Reusken, Cb" uniqKey="Reusken C">CB Reusken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Jf" uniqKey="Chan J">JF Chan</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="To, Kk" uniqKey="To K">KK To</name></author><author><name sortKey="Cheng, Vc" uniqKey="Cheng V">VC Cheng</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name></author><author><name sortKey="Tsang, Ak" uniqKey="Tsang A">AK Tsang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name></author><author><name sortKey="Tsang, Ak" uniqKey="Tsang A">AK Tsang</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author><author><name sortKey="Ithete, Nl" uniqKey="Ithete N">NL Ithete</name></author><author><name sortKey="Richards, Lr" uniqKey="Richards L">LR Richards</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, L" uniqKey="Yang L">L Yang</name></author><author><name sortKey="Wu, Z" uniqKey="Wu Z">Z Wu</name></author><author><name sortKey="Ren, X" uniqKey="Ren X">X Ren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anthony, Sj" uniqKey="Anthony S">SJ Anthony</name></author><author><name sortKey="Gilardi, K" uniqKey="Gilardi K">K Gilardi</name></author><author><name sortKey="Menachery, Vd" uniqKey="Menachery V">VD Menachery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L van der Hoek</name></author><author><name sortKey="Pyrc, K" uniqKey="Pyrc K">K Pyrc</name></author><author><name sortKey="Jebbink, Mf" uniqKey="Jebbink M">MF Jebbink</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Lai, St" uniqKey="Lai S">ST Lai</name></author><author><name sortKey="Poon, Ll" uniqKey="Poon L">LL Poon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Chu, Cm" uniqKey="Chu C">CM Chu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Lam, Cs" uniqKey="Lam C">CS Lam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, Mm" uniqKey="Lai M">MM Lai</name></author><author><name sortKey="Cavanagh, D" uniqKey="Cavanagh D">D Cavanagh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brian, Da" uniqKey="Brian D">DA Brian</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Groot, Rj" uniqKey="De Groot R">RJ de Groot</name></author><author><name sortKey="Baker, Sc" uniqKey="Baker S">SC Baker</name></author><author><name sortKey="Baric, R" uniqKey="Baric R">R Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="De Graaf, M" uniqKey="De Graaf M">M de Graaf</name></author><author><name sortKey="Lauber, C" uniqKey="Lauber C">C Lauber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name></author><author><name sortKey="Qi, J" uniqKey="Qi J">J Qi</name></author><author><name sortKey="Yuan, Y" uniqKey="Yuan Y">Y Yuan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agnarsson, I" uniqKey="Agnarsson I">I Agnarsson</name></author><author><name sortKey="Zambrana Torrelio, Cm" uniqKey="Zambrana Torrelio C">CM Zambrana-Torrelio</name></author><author><name sortKey="Flores Saldana, Np" uniqKey="Flores Saldana N">NP Flores-Saldana</name></author><author><name sortKey="May Collado, Lj" uniqKey="May Collado L">LJ May-Collado</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cai, Y" uniqKey="Cai Y">Y Caì</name></author><author><name sortKey="Yu, Sq" uniqKey="Yu S">SQ Yú</name></author><author><name sortKey="Postnikova, En" uniqKey="Postnikova E">EN Postnikova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Munster, Vj" uniqKey="Munster V">VJ Munster</name></author><author><name sortKey="Adney, Dr" uniqKey="Adney D">DR Adney</name></author><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N van Doremalen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yob, Jm" uniqKey="Yob J">JM Yob</name></author><author><name sortKey="Field, H" uniqKey="Field H">H Field</name></author><author><name sortKey="Rashdi, Am" uniqKey="Rashdi A">AM Rashdi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Yip, Cc" uniqKey="Yip C">CC Yip</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Wernery, R" uniqKey="Wernery R">R Wernery</name></author><author><name sortKey="Wong, Ey" uniqKey="Wong E">EY Wong</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></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, Y" uniqKey="Sun Y">Y Sun</name></author><author><name sortKey="Qi, Y" uniqKey="Qi Y">Y Qi</name></author><author><name sortKey="Liu, C" uniqKey="Liu C">C Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xiong, L" uniqKey="Xiong L">L Xiong</name></author><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author><author><name sortKey="Ye, Yn" uniqKey="Ye Y">YN Ye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, G" uniqKey="Lu G">G Lu</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Liu, C" uniqKey="Liu C">C Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, N" uniqKey="Wang N">N Wang</name></author><author><name sortKey="Shi, X" uniqKey="Shi X">X Shi</name></author><author><name sortKey="Jiang, L" uniqKey="Jiang L">L Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Niemeyer, D" uniqKey="Niemeyer D">D Niemeyer</name></author><author><name sortKey="Zillinger, T" uniqKey="Zillinger T">T Zillinger</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D Muth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thornbrough, Jm" uniqKey="Thornbrough J">JM Thornbrough</name></author><author><name sortKey="Jha, Bk" uniqKey="Jha B">BK Jha</name></author><author><name sortKey="Yount, B" uniqKey="Yount B">B Yount</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cotten, M" uniqKey="Cotten M">M Cotten</name></author><author><name sortKey="Watson, Sj" uniqKey="Watson S">SJ Watson</name></author><author><name sortKey="Zumla, Ai" uniqKey="Zumla A">AI Zumla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sabir, Js" uniqKey="Sabir J">JS Sabir</name></author><author><name sortKey="Lam, Tt" uniqKey="Lam T">TT Lam</name></author><author><name sortKey="Ahmed, Mm" uniqKey="Ahmed M">MM Ahmed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cauchemez, S" uniqKey="Cauchemez S">S Cauchemez</name></author><author><name sortKey="Fraser, C" uniqKey="Fraser C">C Fraser</name></author><author><name sortKey="Van Kerkhove, Md" uniqKey="Van Kerkhove M">MD Van Kerkhove</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Seilmaier, M" uniqKey="Seilmaier M">M Seilmaier</name></author><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hon, Cc" uniqKey="Hon C">CC Hon</name></author><author><name sortKey="Lam, Ty" uniqKey="Lam T">TY Lam</name></author><author><name sortKey="Shi, Zl" uniqKey="Shi Z">ZL Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Feng, Y" uniqKey="Feng Y">Y Feng</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Song, Hd" uniqKey="Song H">HD Song</name></author><author><name sortKey="Tu, Cc" uniqKey="Tu C">CC Tu</name></author><author><name sortKey="Zhang, Gw" uniqKey="Zhang G">GW Zhang</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">J. Infect. Dis</journal-id><journal-id journal-id-type="publisher-id">jid</journal-id><journal-title-group><journal-title>The Journal of Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">0022-1899</issn><issn pub-type="epub">1537-6613</issn><publisher><publisher-name>Oxford University Press</publisher-name><publisher-loc>US</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29346682</article-id><article-id pub-id-type="pmc">7107427</article-id><article-id pub-id-type="doi">10.1093/infdis/jiy018</article-id><article-id pub-id-type="publisher-id">jiy018</article-id><article-categories><subj-group subj-group-type="heading"><subject>Major Articles and Brief Reports</subject><subj-group subj-group-type="category-toc-heading"><subject>Viruses</subject></subj-group></subj-group></article-categories><title-group><article-title>Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lau</surname><given-names>Susanna K P</given-names></name><xref ref-type="aff" rid="AF0001">1</xref><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="aff" rid="AF0003">3</xref><xref ref-type="aff" rid="AF0004">4</xref><xref ref-type="author-notes" rid="fn-0001"></xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Libiao</given-names></name><xref ref-type="aff" rid="AF0005">5</xref><xref ref-type="author-notes" rid="fn-0001"></xref></contrib><contrib contrib-type="author"><name><surname>Luk</surname><given-names>Hayes K H</given-names></name><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="author-notes" rid="fn-0001"></xref></contrib><contrib contrib-type="author"><name><surname>Xiong</surname><given-names>Lifeng</given-names></name><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="author-notes" rid="fn-0001"></xref></contrib><contrib contrib-type="author"><name><surname>Peng</surname><given-names>Xingwen</given-names></name><xref ref-type="aff" rid="AF0005">5</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Kenneth S M</given-names></name><xref ref-type="aff" rid="AF0002">2</xref></contrib><contrib contrib-type="author"><name><surname>He</surname><given-names>Xiangyang</given-names></name><xref ref-type="aff" rid="AF0005">5</xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Pyrear Su-Hui</given-names></name><xref ref-type="aff" rid="AF0002">2</xref></contrib><contrib contrib-type="author"><name><surname>Fan</surname><given-names>Rachel Y Y</given-names></name><xref ref-type="aff" rid="AF0002">2</xref></contrib><contrib contrib-type="author"><name><surname>Wong</surname><given-names>Antonio C P</given-names></name><xref ref-type="aff" rid="AF0002">2</xref></contrib><contrib contrib-type="author"><name><surname>Ahmed</surname><given-names>Syed Shakeel</given-names></name><xref ref-type="aff" rid="AF0002">2</xref></contrib><contrib contrib-type="author"><name><surname>Cai</surname><given-names>Jian-Piao</given-names></name><xref ref-type="aff" rid="AF0002">2</xref></contrib><contrib contrib-type="author"><name><surname>Chan</surname><given-names>Jasper F W</given-names></name><xref ref-type="aff" rid="AF0001">1</xref><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="aff" rid="AF0003">3</xref><xref ref-type="aff" rid="AF0004">4</xref></contrib><contrib contrib-type="author"><name><surname>Sun</surname><given-names>Yinyan</given-names></name><xref ref-type="aff" rid="AF0006">6</xref></contrib><contrib contrib-type="author"><name><surname>Jin</surname><given-names>Dongyan</given-names></name><xref ref-type="aff" rid="AF0007">7</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Honglin</given-names></name><xref ref-type="aff" rid="AF0001">1</xref><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="aff" rid="AF0003">3</xref><xref ref-type="aff" rid="AF0004">4</xref></contrib><contrib contrib-type="author"><name><surname>Lau</surname><given-names>Terrence C K</given-names></name><xref ref-type="aff" rid="AF0008">8</xref></contrib><contrib contrib-type="author"><name><surname>Kok</surname><given-names>Raven K H</given-names></name><xref ref-type="aff" rid="AF0001">1</xref><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="aff" rid="AF0003">3</xref><xref ref-type="aff" rid="AF0004">4</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Wenhui</given-names></name><xref ref-type="aff" rid="AF0006">6</xref></contrib><contrib contrib-type="author"><name><surname>Yuen</surname><given-names>Kwok-Yung</given-names></name><xref ref-type="aff" rid="AF0001">1</xref><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="aff" rid="AF0003">3</xref><xref ref-type="aff" rid="AF0004">4</xref></contrib><contrib contrib-type="author"><name><surname>Woo</surname><given-names>Patrick C Y</given-names></name><xref ref-type="aff" rid="AF0001">1</xref><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="aff" rid="AF0003">3</xref><xref ref-type="aff" rid="AF0004">4</xref><xref ref-type="corresp" rid="c1"></xref><pmc-comment>pcywoo@hku.hk </pmc-comment>
</contrib></contrib-group><aff id="AF0001"><label>1</label>State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China</aff><aff id="AF0002"><label>2</label>Department of Microbiology The University of Hong Kong, China</aff><aff id="AF0003"><label>3</label>Carol Yu Centre for Infection The University of Hong Kong, China</aff><aff id="AF0004"><label>4</label>Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China</aff><aff id="AF0005"><label>5</label>Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, and Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong Province, China</aff><aff id="AF0006"><label>6</label>National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, Beijing, China</aff><aff id="AF0007"><label>7</label>School of Biomedical Sciences, The University of Hong Kong, China</aff><aff id="AF0008"><label>8</label>Department of Biomedical Sciences, City University of Hong Kong, China</aff><author-notes><fn id="fn-0001"><p>S. K. P. L., L.. Z., H. K. H. L., and L. X. contributed equally to the manuscript.</p></fn><corresp id="c1">Correspondence: P. C. Y. Woo, MD, State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Room 423, University Pathology Building, Queen Mary Hospital, Hong Kong, China (<email>pcywoo@hku.hk</email>).</corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>7</month><year>2018</year></pub-date><pub-date pub-type="epub" iso-8601-date="2018-01-16"><day>16</day><month>1</month><year>2018</year></pub-date><pub-date pub-type="pmc-release"><day>20</day><month>6</month><year>2019</year></pub-date><pmc-comment> PMC Release delay is 12 months and
0 days and was based on the
<volume>218</volume><issue>2</issue><fpage>197</fpage><lpage>207</lpage><history><date date-type="received"><day>20</day><month>11</month><year>2017</year></date><date date-type="accepted"><day>15</day><month>1</month><year>2018</year></date></history><permissions><copyright-statement>© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</copyright-statement><copyright-year>2018</copyright-year><license license-type="oup-standard" xlink:href="https://academic.oup.com/journals/pages/about_us/legal/notices"><license-p>This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (<ext-link ext-link-type="uri" xlink:href="https://academic.oup.com/journals/pages/about_us/legal/notices">https://academic.oup.com/journals/pages/about_us/legal/notices</ext-link>)</license-p></license><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.</license-p></license></permissions><self-uri xlink:href="jiy018.pdf"></self-uri><abstract abstract-type="teaser"><p>The discovery of Hp-BatCoV HKU25 bridges the evolutionary gap between MERS-CoV and existing bat viruses, and suggests that bat viruses may have evolved to generate MERS-CoV through modulation of the spike protein for binding to hDPP4.</p></abstract><abstract><title>Abstract</title><p>Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4.</p></abstract><kwd-group><kwd>dipeptidyl peptidase 4</kwd><kwd><italic>Hypsugo</italic> bat</kwd><kwd>Middle East Respiratory Syndrome coronavirus</kwd><kwd>spike glycoprotein</kwd></kwd-group><funding-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">Theme-Based Research Scheme</named-content></funding-source><award-id>T11-707/15-R</award-id></award-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">Research Grant Council Grant, University Grant Council</named-content></funding-source></award-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">Health and Medical Research Fund</named-content><named-content content-type="funder-identifier">10.13039/501100005847</named-content></funding-source><award-id>13121102</award-id></award-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">Food and Health Bureau of Hong Kong Special Administrative Region</named-content></funding-source></award-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">Croucher Senior Medical Research Fellowships</named-content></funding-source></award-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">Committee for Research and Conference Grant</named-content></funding-source></award-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">Strategic Research Theme Fund</named-content></funding-source></award-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">The University of Hong Kong</named-content></funding-source></award-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Disease for the HKSAR Department of Health</named-content></funding-source></award-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">National Science and Technology Major Project of China</named-content></funding-source><award-id>2012ZX10004213</award-id></award-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">GDAS Special Project of Science and Technology Development</named-content></funding-source><award-id>2017GDASCX-0107</award-id></award-group></funding-group><counts><page-count count="11"></page-count></counts></article-meta></front><body><p>The Middle East Respiratory Syndrome (MERS) has affected 27 countries in 4 continents with 2090 cases and a fatality rate of 34.9% since its emergence in 2012. The etiological agent, MERS coronavirus (MERS-CoV), belongs to <italic>Betacoronavirus</italic> lineage C [<xref rid="CIT0001" ref-type="bibr">1</xref>, <xref rid="CIT0002" ref-type="bibr">2</xref>] and uses human dipeptidyl peptidase 4 (hDPP4) as receptor for cell entry [<xref rid="CIT0003" ref-type="bibr">3</xref>]. Although dromedaries are likely the immediate animal source of the epidemic [<xref rid="CIT0004" ref-type="bibr">4–6</xref>], bats also harbor MERS-CoV-related viruses, which suggests a possible bat origin [<xref rid="CIT0007" ref-type="bibr">7–13</xref>]. However, the evolutionary pathway and direct ancestor of MERS-CoV remains obscure. In particular, there is an evolutionary gap between MERS-CoV and related bat viruses.</p><p>Since the severe acute respiratory syndrome (SARS) epidemic, numerous novel CoVs have been discovered [<xref rid="CIT0014" ref-type="bibr">14–16</xref>], with bats uncovered as an important reservoir for alphacoronaviruses and betacoronaviruses [<xref rid="CIT0017" ref-type="bibr">17–21</xref>]. When MERS-CoV was first discovered, it was most closely related to <italic>Tylonycteris</italic> bat CoV HKU4 (Ty-BatCoV HKU4) and <italic>Pipistrellus</italic> bat CoV HKU5 (Pi-BatCoV HKU5) previously discovered in the Lesser bamboo bat (<italic>Tylonycteris pachypus</italic>) and Japanese pipistrelle (<italic>Pipistrellus abramus</italic>), respectively, in Hong Kong [<xref rid="CIT0001" ref-type="bibr">1</xref>, <xref rid="CIT0007" ref-type="bibr">7–10</xref>, <xref rid="CIT0022" ref-type="bibr">22</xref>]. The spike of Ty-BatCoV HKU4, but not that of Pi-BatCoV HKU5, was able to use the MERS-CoV receptor, hDPP4 or CD26, for cell entry [<xref rid="CIT0003" ref-type="bibr">3</xref>, <xref rid="CIT0023" ref-type="bibr">23</xref>]. Subsequently, 3 other lineage C betacoronaviruses (Coronavirus Neoromicia/PML-PHE1/RSA/2011 [NeoCoV], BtVs-BetaCoV/SC2013, and BatCoV PREDICT/PDF-2180) were also detected in vesper bats from China or Africa [<xref rid="CIT0011" ref-type="bibr">11–13</xref>, <xref rid="CIT0024" ref-type="bibr">24</xref>]. A lineage C betacoronavirus, Erinaceus CoV VMC/DEU, has also been found in European hedgehogs [<xref rid="CIT0025" ref-type="bibr">25</xref>]. This is interesting because hedgehogs are phylogenetically closely related to bats. The MERS-CoV can infect bat cell lines and Jamaican fruit bats [<xref rid="CIT0025" ref-type="bibr">25</xref>, <xref rid="CIT0026" ref-type="bibr">26</xref>], further suggesting that bats may be the primary host of MERS-CoV ancestors.</p><p>Although NeoCoV represents the closest bat counterpart of MERS-CoV in most genome regions, its spike (S) protein is genetically divergent from that of MERS-CoV [<xref rid="CIT0011" ref-type="bibr">11</xref>], suggesting an evolutionary gap between existing MERS-CoV and bat viruses and an immediate ancestor of MERS-CoV yet to be discovered. To identify the potential bat origin and understand the evolutionary path of MERS-CoV, we collected bat samples from various regions in China. Diverse CoVs were detected, including a novel lineage C betacoronavirus from Chinese pipistrelle (<italic>Hypsugo pulveratus</italic>), which can use hDPP4 for cell entry. The results support a bat origin of MERS-CoV and suggested stepwise evolution of spike protein in hDPP4 binding.</p><sec sec-type="materials|methods" id="s1"><title>MATERIALS AND METHODS</title><sec id="s2"><title>Ethics Statement</title><p>Bat samples were collected by the Guangdong Institute of Applied Biological Resources (Guangzhou, China) in accordance with guidelines of Regulations for Administration of Laboratory Animals under a license from Guangdong Entomological Institute Administrative Panel on Laboratory Animal Care.</p></sec><sec id="s3"><title>Detection of Coronavirus From Bats</title><p>Samples were collected from bats captured from various locations in 7 provinces of China (<xref ref-type="fig" rid="F1">Figure 1</xref>) during 2013−2015 using procedures described previously [<xref rid="CIT0027" ref-type="bibr">27</xref>, <xref rid="CIT0028" ref-type="bibr">28</xref>]. Viral ribonucleic acid (RNA) extraction was performed using QIAamp Viral RNA Mini Kit (QIAGEN, Hilden, Germany). Coronavirus detection was performed by reverse-transcription polymerase chain reaction (RT-PCR) targeting a 440-base pair (bp) fragment of RNA-dependent RNA polymerase (RdRp) gene using conserved primers (5’-GGTTGGGACTATCCTAAGTGTGA-3’ and 5’-ACCATCATCNGANARDATCATNA-3’) as described previously [<xref rid="CIT0016" ref-type="bibr">16</xref>]. A phylogenetic tree was constructed with maximum likelihood method using GTR+G+I substitution model by MEGA 6.0.</p><fig fig-type="figure" id="F1" orientation="portrait" position="float"><label>Figure 1.</label><caption><p>Map showing various sampling locations in seven provinces of China (Guangxi, Guangdong, Shanxi, Zhejiang, Yunnan, Hainan and Guizhou). Sampling locations with Hp-BatCoV HKU25 and other CoVs detected are indicated with triangle and diamond respectively.</p></caption><graphic xlink:href="jiy01801"></graphic></fig></sec><sec id="s4"><title>Viral Culture</title><p>The 2 Hp-BatCoV HKU25 samples were subject to virus isolation in Vero E6 (ATCC CRL-1586), Huh-7 (JCRB0403), PK15 (ATCC CCL-33), and <italic>Rousettus lechenaultii</italic> primary kidney cells (in-house) as described previously [<xref rid="CIT0029" ref-type="bibr">29</xref>].</p></sec><sec id="s5"><title>Complete Genome Sequencing and Analysis of <italic>Hypsugo pulveratus</italic> Bat Coronavirus HKU25</title><p>Two Hp-BatCoV HKU25 complete genomes were sequenced according to our published strategy [<xref rid="CIT0027" ref-type="bibr">27</xref>]. A total of 75 sets of primers, available on request, were used for PCR. The assembled genome sequences were compared with those of other CoVs using the comprehensive CoV database CoVDB (<ext-link ext-link-type="uri" xlink:href="http://covdb.microbiology.hku.hk">http://covdb.microbiology.hku.hk</ext-link>) [<xref rid="CIT0030" ref-type="bibr">30</xref>]. The time of the most recent common ancestor (tMRCA) was estimated based on ORF1ab sequences, using uncorrelated exponential distributed relaxed clock model in BEAST version 1.8 (<ext-link ext-link-type="uri" xlink:href="http://evolve.zoo.ox.ac.uk/beast/">http://evolve.zoo.ox.ac.uk/beast/</ext-link>) [<xref rid="CIT0031" ref-type="bibr">31</xref>].</p></sec><sec id="s6"><title>Cloning of Recombinant S1 Receptor-Binding Domain Proteins</title><p>The S1-RBD sequences of of Hp-BatCoV HKU25 (residues 374–604) and MERS-CoV (residues 367–606) were cloned into mammalian expression vector pCAGGS containing signal peptide (CD5) and C-terminal Fc tag from mouse IgG2a (mFc) [<xref rid="CIT0032" ref-type="bibr">32</xref>, <xref rid="CIT0033" ref-type="bibr">33</xref>]. The expression plasmids were transiently transfected into human embryonic kidney HEK293T cells (American Type Culture Collection CRL-3216). The recombinant HKU25-RBD-mFc and MERS-RBD-mFc proteins were purified by protein A-based affinity chromatography.</p></sec><sec id="s7"><title>Protein Binding with Flow Cytometry and Fluorescence-Activated Cell Sorter Analysis</title><p>Huh7 (normal or DPP4 knockdown using small interfering RNA [siRNA]) or 293T (normal or transfected with DPP4-expressing plasmid) cells were incubated with 10 μg/mL MERS-RBD-mFc or 40 µg/mL HKU25-RBD-mFc at 4°C for 1 hour. Cells were then stained with Alexa Fluor 488-conjugated goat antimouse IgG on ice for 30 minutes. Protein-to-cell binding was analyzed using BD fluorescence-activated cell sorter (FACS) LSRII instrument (BD Bioscience, East Rutherford, NJ).</p></sec><sec id="s8"><title>Immunostaining and Confocal Microscopy</title><p>Huh7 cells were fixed on glass coverslips and incubated with 50 μg/mL HKU25-RBD-mFc or 20 µg/mL MERS-RBD-mFc in phosphate-buffered saline at 4°C for 1 hour, followed by staining with Alexa Fluor 488-conjugated goat antimouse or anti-rabbit IgG. Cell nuclei were stained using 4’,6-diamidino-2-phenylindole in mounting medium. Images were acquired with 63× oil objectives using a Zeiss LSM510 Meta laser scanning confocal microscope.</p></sec><sec id="s9"><title>Knockdown of Human Dipeptidyl Peptidase 4 Expression Using Small Interfering Ribonucleic Acids</title><p>The siRNA duplexes against hDPP4 (5′-UGACAUGCCUC AGUUGUAUU-3′) were synthesized by Nucleic Acids Center at National Institute of Biological Sciences (Beijing, China), with nontargeting siRNA as negative control (Ctrl-si). Ten picomoles of siRNA were transfected into Huh7 cells with Lipofectamine RNAiMax (Invitrogen). Knockdown efficiency was determined by quantitative RT-PCR analysis using primers specific for hDPP4 (5′-CCTGCTTCTATGTTGATA-3′; 5′-CGAATAGTTCTGAATCCT-3′) and Western blot analysis using anti-hDPP4 antibody (Abcam, Cambridge, United Kingdom). The messenger RNA (mRNA) levels of target genes were normalized to that of the glyceraldehyde 3-phosphate dehydrogenase (<italic>gapdh</italic>) gene [<xref rid="CIT0034" ref-type="bibr">34</xref>].</p></sec><sec id="s10"><title>Immunoprecipitation</title><p>To identify the direct interaction between MERS-RBD-mFc or HKU25-RBD-mFc and hDPP4, HEK293T cells were transfected with hDPP4-expressing plasmids and lysed with radioimmunoprecipitation assay buffer containing 1× protease inhibitor cocktail (Roche) 48 hours after transfection. Cell lysates were incubated with purified MERS-RBD-mFc or HKU25-RBD-mFc and Dynal protein A Sepharose beads at 4°C overnight. The bound fractions of immunoprecipitates and total cell lysate (as input) were analyzed by Western blot with anti-mFc, anti-hDPP4, or anti-GAPDH antibodies.</p></sec><sec id="s11"><title>Pseudovirus Production</title><p>Retroviruses pseudotyped with MERS-CoV, Ty-BatCoV HKU4, Pi-BatCoV HKU5, and Hy-BatCoV HKU25 S proteins were packaged by HEK293FT cells (R70007; Invitrogen). Briefly, plasmid containing the respective CoV S gene was cotransfected with a plasmid containing luciferase gene but env-defective human immunodeficiency virus-1 (pNL 4-3.Luc.RE) into 293FT cells using Lipofectamine 2000 (Invitrogen). Culture supernatant was concentrated with 5× PEG-it virus precipitation solution (SBI). For mock pseudoviruses (∆env) bearing no S protein, empty plasmid was cotransfected with pNL 4-3.Luc.RE.</p></sec><sec id="s12"><title>Pseudovirus Cell Entry Assay</title><p>HEK293T cells were transfected with plasmid containing hDPP4 gene and empty plasmid (as mock-transfected control) by Lipofectamine 2000. Pseudoviruses bearing CoV S proteins were treated by 100 µg/mL Tosyl phenylalanyl chloromethyl ketone-treated trypsin at 37°C for 30 minutes before infection. After trypsin inactivation, pseudovirus infections were performed by spinning at 1200 ×<italic>g</italic> at 4°C for 2 hours and incubation at 37°C for 5 hours. Cells were then incubated for 72 hours and lysed for luciferase activity determination using Luciferase Assay System (Promega, Fitchburg, WI). To test for inhibition of pseudovirus-mediated cell entry by anti-hDPP4 antibodies, HEK293T cells transfected with hDPP4 were preincubated with 10 µg/mL anti-hDPP4 polyclonal antibodies (R&D Systems) at 37°C for 1 hour before pseudovirus infection.</p></sec><sec id="s13"><title>Structural Modeling of <italic>Hypsugo pulveratus</italic> Bat Coronavirus HKU25 Receptor-Binding Domain</title><p>The model of HKU25-RBD and HKU5-RBD was built with the crystal structure of MERS-RBD/hDPP4 using SWISS-MODEL with default parameters and analyzed using Discovery Studio visualizer (Accelrys, San Diego, CA), and the Ramachandran plots were examined to ensure that the structure of the models were not in any unfavorable region. The models of HKU4-RBD and HKU5-RBD were also built as positive and negative controls, respectively, with the same parameters, and were superimposed for comparison.</p></sec><sec id="s14"><title>Nucleotide Sequence Accession Numbers</title><p>The nucleotide (nt) and genome sequences of CoVs detected in this study have been lodged within GenBank under accession numbers KX442564, KX442565, and KX447541 to KX447565.</p></sec></sec><sec id="s15"><title>RESULTS</title><sec id="s16"><title>Detection of Coronavirus in Bats and Discovery of a Novel Lineage C Betacoronavirus From Chinese Pipistrelle</title><p>A total of 1964 alimentary samples from bats belonging to 19 different genera and 44 species were obtained from 7 provinces of China. The RT-PCR for a 440-bp fragment of RdRp gene of CoVs was positive in samples from 29 bats of 5 species belonging to 4 genera (<xref ref-type="fig" rid="F1">Figure 1</xref> and <xref ref-type="supplementary-material" rid="sup1">Supplementary Table 1</xref>). Sequence analysis showed that 4 samples contained alphacoronaviruses, 5 contained lineage B betacoronaviruses, and 20 contained lineage C betacoronaviruses (<xref ref-type="supplementary-material" rid="sup6">Supplementary Figure 1</xref>).</p><p>Of the 20 lineage C betacoronavirus sequences, 18 sequences from <italic>Tylonycteris pachypus</italic> possessed 96% nt identities to Ty-BatCoV HKU4. The other 2 lineage C betacoronavirus sequences (YD131305 and NL140462) showed ≤86% nt identities to MERS-CoV or other lineage C betacoronaviruses, suggesting a potentially novel lineage C betacoronavirus closely related to MERS-CoV (<xref ref-type="supplementary-material" rid="sup1">Supplementary Table 1</xref> and <xref ref-type="supplementary-material" rid="sup6">Supplementary Figure 1</xref>). Both samples were collected from Chinese pipistrelle (<italic>Hypsugo pulveratus</italic>) bats, which belong to the family Vespertilionidae, captured in Guangdong Province (<xref ref-type="fig" rid="F1">Figure 1</xref>). We proposed this novel CoV to be named <italic>Hypsugo pulveratus</italic> bat CoV HKU25 (Hp-BatCoV HKU25). Attempts to passage Hp-BatCoV HKU25 YD131305 and NL140462 in cell cultures were not successful.</p></sec><sec id="s17"><title>Genome Features of <italic>Hypsugo pulveratus</italic> Bat Coronavirus HKU25</title><p>The complete genome sequences of the 2 Hp-BatCoV HKU25 strains, YD131305 and NL140462, were determined, with genome features similar to MERS-CoV including conserved ORF4a and ORF4b (<xref ref-type="supplementary-material" rid="sup2">Supplementary Table 2</xref>, <xref ref-type="supplementary-material" rid="sup4">Supplementary Table 4</xref>, <xref ref-type="supplementary-material" rid="sup7">Supplementary Figure 2</xref>, and <xref ref-type="supplementary-material" rid="sup8">Supplementary Figure 3</xref>). They shared 95.9% overall nt identities, while possessing 82.0%, 73.2%–73.9%, 73.5%, and 69.3% nt identities to the genomes of BtVs-BetaCoV/SC2013, human/camel MERS-CoVs, NeoCoV, and Ty-BatCoV HKU4, respectively. Comparison of the 7 conserved replicase domains for CoV species demarcation showed that Hp-BatCoV HKU25 represents a novel species under <italic>Betacoronavirus</italic> lineage C (<xref ref-type="supplementary-material" rid="sup5">Supplementary Table 5</xref>), with the concatenated sequence being most closely related to that of BtVs-BetaCoV/SC2013 with 88.5% amino acid (aa) identities.</p></sec><sec id="s18"><title>Phylogenetic and Molecular Clock Analysis</title><p>Phylogenetic trees constructed using RdRp, ORF1, S1, and N sequences of Hp-BatCoV HKU25 are shown in <xref ref-type="fig" rid="F2">Figure 2</xref>. Hp-BatCoV HKU25 was most closely related to BtVs-BetaCoV/SC2013, forming a distinct branch among lineage C betacoronaviruses. In RdRp, ORF1, and N genes, MERS-CoVs were most closely related to NeoCoV followed by the branch formed by Hp-BatCoV HKU25 and BtVs-BetaCoV/SC2013. In contrast, in S1 region, MERS-CoVs were most closely related to Ty-BatCoV HKU4, followed by the branch formed by Hp-BatCoV HKU25 and BtVs-BetaCoV/SC2013, but was only distantly related to NeoCoV. Thus, Hp-BatCoV HKU25 and BtVs-BetaCoV/SC2013 represent close relatives of MERS-CoV, while they occupied a position in between Ty-BatCoV HKU4 and Pi-BatCoV HKU5 in relation to MERS-CoV in S1 region.</p><fig fig-type="figure" id="F2" orientation="portrait" position="float"><label>Figure 2.</label><caption><p>Phylogenetic analyses of RdRp, ORF1, S1 and N nucleotide sequences of Hp-BatCoV HKU25 and other lineage C betacoronaviruses (B). The trees were constructed by maximum likelihood method using GTR+G substitution models respectively and bootstrap values calculated from 1000 trees. Trees were rooted using corresponding sequences of HCoV HKU1 (GenBank accession number NC_006577). Only bootstrap values >70% are shown. (A) 2775 nt (B) 20694 nt (C) 3740 nt (D) 1167 nt positions respectively were included in the analyses. The scale bars represent (A) 20 (B) 20 (C) 10 (D) 10 substitutions per site respectively. The two Hp-BatCoV HKU25 strains, YD131305 and NL140462, detected in this study are bolded and underlined.</p></caption><graphic xlink:href="jiy01802"></graphic></fig><p>Using the uncorrelated relaxed clock model on ORF1ab, tMRCA of human and camel MERS-CoVs was dated to 2009.56 (highest posterior density [HPD], 2006.8−2011.3), whereas that of MERS-CoV, NeoCoV, Hp-BatCoV HKU25, and BtVs-BetaCoV/SC2013 was dated to 1939.32 (HPDs, 1899.5−1969.0) (<xref ref-type="supplementary-material" rid="sup9">Supplementary Figure 4</xref>).</p></sec><sec id="s19"><title>Sequence Analysis of <italic>Hypsugo pulveratus</italic> Bat Coronavirus Spike Protein</title><p>The MERS-CoV uses hDPP4, a type II transmembrane protein, as receptor for initiation of infection [<xref rid="CIT0003" ref-type="bibr">3</xref>]. The S1 domain responsible for hDPP4 receptor binding is located in a C-terminal 240-residue RBD that contains the receptor-binding motif, which engages the receptor [<xref rid="CIT0035" ref-type="bibr">35</xref>]. Using binding and pseudovirus assays, it was shown that Ty-BatCoV HKU4 S, but not Pi-BatCoV HKU5 S, can bind to and use hDPP4 for cell entry [<xref rid="CIT0023" ref-type="bibr">23</xref>, <xref rid="CIT0036" ref-type="bibr">36</xref>]. Because phylogenetic analysis placed Hp-BatCoV HKU25-S1 at a position between Ty-BatCoV HKU4 and Pi-BatCoV HKU5 in relation to MERS-CoV, it would be interesting to know whether Hp-BatCoV HKU25 may bind to and use hDPP4 for cell entry. As in other CoVs, Hp-BatCoV HKU25-S is predicted to be a type I membrane glycoprotein with 2 heptad repeats. The predicted Hp-BatCoV HKU25-S1-RBD shared 53.5% aa identities to that of MERS-CoV, with 2 short deletions compared with MERS-CoV and Ty-BatCoV HKU4 (<xref ref-type="fig" rid="F3">Figure 3</xref>).</p><fig fig-type="figure" id="F3" orientation="portrait" position="float"><label>Figure 3.</label><caption><p>Multiple alignment of the amino acid sequences of the receptor-binding domain (RBD) of the spike protein of MERS-CoV and corresponding sequences in Hp-BatCoV HKU25 and other lineage C betacoronaviruses. Asterisks indicate positions with fully conserved residues. The two amino acid deletions in Hp-BatCoV HKU25 compared to MERS-CoV and Ty-BatCoV HKU4 are indicated with boxes. The 12 critical residues for receptor binding in MERS-CoV are highlighted. The 10 residues marked below the alignment are based on (Wang, 2013) [<xref rid="CIT0037" ref-type="bibr">37</xref>] and the other two residues marked above the alignment are based on (Wang, 2014) [<xref rid="CIT0023" ref-type="bibr">23</xref>]. Y499 formed hydrogen bond with DPP4 residue. L506, W553 and V555 formed a hydrophobic core surrounded by hydrophilic residues D510, E513 and Y540. D510 and E513 also contributed to salt bridge interaction and hydrogen bonding with DPP4 residues. E536, D537 and D539 formed negative-charged surface. W535 and R542 are residues that have strong polar contact with DPP4 residues.</p></caption><graphic xlink:href="jiy01803"></graphic></fig><p>Previous structural studies have identified 12 critical residues (Y499, L506, D510, E513, W535, E536, D537, D539, Y540, R542, W553, and V555) for hDPP4 binding in MERS-CoV [<xref rid="CIT0023" ref-type="bibr">23</xref>, <xref rid="CIT0037" ref-type="bibr">37</xref>]. In Ty-BatCoV HKU4, 5 (Y503, L510, E518, E541, and D542 corresponding to Y499, L506, E513, E536, and D537 in MERS-RBD) residues were conserved, which may allow binding to hDPP4. In Pi-BatCoV HKU5, 1 of the 12 conserved residues (D543 corresponding to D537 in MERS-RBD) was found. In Hp-BatCoV HKU25, 1 residue (R546 in strain YD131305/R547 in strain NL140462 corresponding to R542 in MERS-RBD) was conserved in both strains, and an additional residue (V554 corresponding to V555 in MERS-RBD) was conserved in strain NL140462 (<xref ref-type="fig" rid="F3">Figure 3</xref>).</p></sec><sec id="s20"><title><italic>Hypsugo pulveratus</italic> Bat Coronavirus (CoV) HKU25-S1-Receptor-Binding Domain (S1-RBD) Binds Human Dipeptidyl Peptidase 4 but With Lower Efficiency Than Middle East Respiratory Syndrome CoV S1-RBD</title><p>To examine the ability of Hp-BatCoV HKU25-S to bind hDPP4, we expressed and purified hDPP4 and the S1-RBD domains of Hp-BatCoV HKU25 (residues 374−604) and MERS-CoV (residues 367−606) using procedures described previously [<xref rid="CIT0032" ref-type="bibr">32</xref>, <xref rid="CIT0033" ref-type="bibr">33</xref>]. We first tested the binding efficiency of the S1-RBD domains to Huh7 cells (human hepatocellular carcinoma cells with endogenous hDPP4 expression) using flow cytometry. The HKU25-RBD can bind to Huh7 cells, although the observed fluorescence shift was smaller than MERS-RBD (<xref ref-type="fig" rid="F4">Figure 4A</xref>). This indicates that HKU25-RBD can bind to hDPP4-expressing Huh7 cells with lower binding efficiency than that of MERS-RBD. To confirm that the binding is mediated by hDPP4, we obtained Huh7 cells with siRNA knockdown of hDPP4 (confirmed by mRNA expression and Western blot) (<xref ref-type="fig" rid="F4">Figure 4C</xref>). A significant reduction of fluorescence shift was observed in both HKU25-RBD- and MERS-RBD-mediated binding to hDPP4-knockdown Huh7 cells compared with hDPP4-expressing Huh7 cells (<xref ref-type="fig" rid="F4">Figure 4A</xref>). Moreover, HKU25-RBD and MERS-RBD could only bind to HEK293T cells (lacking endogenous hDPP4 expression) after transfection with hDPP4-expressing plasmid, although the binding efficiency to hDPP4-expressing HEK293T cells was lower for HKU25-RBD than MERS-RBD (<xref ref-type="fig" rid="F4">Figure 4B</xref>). Second, we also confirmed the binding of HKU25-RBD to Huh7 cell surface by confocal microscopy (<xref ref-type="fig" rid="F4">Figure 4D</xref>). Third, immunoprecipitation assays showed that hDPP4 protein can be specifically pulled down by both MERS-RBD and HKU25-RBD (<xref ref-type="fig" rid="F5">Figure 5</xref>). These results indicated that HKU25-RBD can bind to hDPP4 on cell surface but with lower efficiency than MERS-CoV-RBD.</p><fig fig-type="figure" id="F4" orientation="portrait" position="float"><label>Figure 4.</label><caption><p>Binding of HKU25-RBD with human cells was mediated by interacting with human dipeptidyl peptidase 4 (hDPP4) receptor. (A) Fluorescence-activated cell sorter (FACS) analysis of Middle East Respiratory Syndrome receptor-binding domain (MERS-RBD)-mFc (10 µg/mL) and HKU25-RBD-mFc (40 µg/mL) binding to Huh7 cells and hDPP4-knockdown Huh7 cells. (B) FACS analysis of MERS-RBD-mFc and HKU25-RBD-mFc binding to 293T cells and 293T cells transfected with hDPP4-expressing plasmid. The shaded area represents the secondary antibody control. (C) Determination of small interfering ribonucleic acid (siRNA) efficiency by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analysis using primers and antibody specific for hDPP4. (D) MERS-RBD-mFc and HKU25-RBD-mFc binding to a molecule(s) located on the Huh7 cell surface. MERS-RBD-mFc and HKU25-RBD-mFc were detected by an Alexa Fluor 488-conjugated goat anti-mFc antibody. Empty expressing plasmid was used as a negative control.</p></caption><graphic xlink:href="jiy01804"></graphic></fig><fig fig-type="figure" id="F5" orientation="portrait" position="float"><label>Figure 5.</label><caption><p>Middle East Respiratory Syndrome receptor-binding domain (MERS-RBD)-mFc (A) and HKU25-RBD-mFc (B) proteins directly bind with human dipeptidyl peptidase 4 (hDPP4). HEK293 T cells were transfected with hDPP4-expressing plasmids, and MERS-RBD-mFc (A) and HKU25-RBD-mFc (B) proteins were used for immunoprecipitation of lysates of HEK293 T cells transfected with hDPP4-expressing or empty plasmids. Empty plasmid was mock-transfected as negative control. The hDPP4 was coprecipitated from the lysates, as detected by antibody specific for hDPP4. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as a loading control.</p></caption><graphic xlink:href="jiy01805"></graphic></fig></sec><sec id="s21"><title>HKU25 Pseudovirus Can Use Human Dipeptidyl Peptidase 4 for Cell Entry but With Lower Infection Efficiency Than Middle East Respiratory Syndrome and HKU4 Pseudoviruses</title><p>To determine whether Hp-BatCoV HKU25-S can mediate viral entry into hDPP4-expressing human cells, we performed HKU25-S-mediated pseudovirus entry assay. Because the S protein of Ty-BatCoV HKU4 but not that of Pi-BatCoV HKU5 can use hDPP4 for cell entry [<xref rid="CIT0036" ref-type="bibr">36</xref>], we included HKU4-S-, HKU5-S-, and MERS-S-mediated pseudovirus entry assays for comparison. Pseudovirus assays were used because isolation of live Hp-BatCoV HKU25 was not successful, as with most bat CoVs that are often difficult to culture. Retroviruses pseudotyped with luciferase and the respective S proteins were tested for entry to HEK293T cells with or without hDPP4 expression. The MERS-S most robustly mediated pseudovirus entry into hDDP4-expressing HEK293T cells, followed by HKU4-S and HKU25-S, as shown by luciferase activities measured. All 3 pseudoviruses showed a marked increase in luciferase activities in hDDP4-expressing HEK293T cells compared with cells without hDPP4 expression (<xref ref-type="fig" rid="F6">Figure 6</xref>). Moreover, anti-hDPP4 polyclonal antibodies could competitively block HKU25-S, HKU4-S, and MERS-S pseudovirus entry to hDPP4-expresssing HEK293T cells, further confirming the binding specificity. In contrast, HKU5-S and control retroviruses not pseudotyped with S did not mediate pseudovirus entry into hDPP4-expressing HEK293T cells (<xref ref-type="fig" rid="F6">Figure 6</xref>). These results showed that hDPP4 is a possible functional receptor for Hp-BatCoV HKU25, although cell entry may be less efficient than Ty-BatCoV HKU4 and MERS-CoV.</p><fig fig-type="figure" id="F6" orientation="portrait" position="float"><label>Figure 6.</label><caption><p>HEK293 T cells transfected with empty plasmid or human dipeptidyl peptidase 4 (hDPP4) were infected by retroviruses pseudotyped with Middle East Respiratory Syndrome coronavirus (MERS-CoV), Ty-BatCoV HKU4, Pi-BatCoV HKU5, and Hp-BatCoV HKU25 S proteins with mock pseudovirus (∆env) as control. The cells were also preincubated with anti-hDPP4 antibodies (Ab) to test for cell entry inhibition. Cell entry efficiencies were assayed by luciferase activity measurement after 72 hours.</p></caption><graphic xlink:href="jiy01806"></graphic></fig></sec><sec id="s22"><title>Structural Modeling of Receptor Binding Domain Human Dipeptidyl Peptidase 4 Binding Interphase</title><p>To predict the RBD-hDPP4 binding interface, the structures of HKU25-, MERS-, HKU4-, and HKU5-RBDs were modeled with that of hDPP4 using homology modeling. The sequence identity between HKU25-RBD and MERS-RBD (template) was >50%, and the RBD-hDPP4 interface for all RBDs was similar (<xref ref-type="supplementary-material" rid="sup10">Supplementary Figure 5</xref>), except that only MERS-RBD and HKU4-RBD possess the extended loop between β6 and β7 involved in interaction with hDPP4 [<xref rid="CIT0023" ref-type="bibr">23</xref>]. A negative-charge residue, E536, located in MERS-RBD, corresponding to E541 in HKU4-RBD, can interact with the carbohydrate moiety of hDPP4, whereas HKU5-RBD contains a positive-charge residue, R542, and HKU25-RBD contains an uncharged residue, T540/A541, at the corresponding position. These findings supported that the binding of HKU25-RBD to hDPP4 may be weaker than that of MERS-RBD and HKU4-RBD but stronger than that of HKU5-RBD.</p></sec></sec><sec id="s23"><title>DISCUSSION</title><p>The novel lineage C betacoronavirus, Hp-BatCoV HKU25, helps to fill the evolutionary gap between existing bat viruses and MERS-CoV, and it offers new insights into the evolutionary origin of MERS-CoV. Hp-BatCoV HKU25 shared similar genome features with MERS-CoV, including the conserved ORF4a and ORF4b with predicted domains for double-stranded RNA binding and antagonizing interferon signals, respectively [<xref rid="CIT0038" ref-type="bibr">38</xref>, <xref rid="CIT0039" ref-type="bibr">39</xref>]. Phylogenetically, Hp-BatCoV HKU25, together with BtVs-BetaCoV/SC2013, was closely related to MERS-CoV and NeoCoV in most genome regions, suggesting that these viruses share a common ancestral origin. Although the S1 of NeoCoV is only distantly related to MERS-CoV, the S1 of Hp-BatCoV HKU25 was at a phylogenetic position closely related to MERS-CoV, only second to Ty-BatCoV HKU4. On the other hand, the S1 of NeoCoV is most closely related to <italic>Erinaceus</italic> CoV from European hedgehogs. Because NeoCoV was detected in an African bat, it is more likely a recombinant virus between bat and hedgehog CoVs in Africa. Moreover, it was shown that the S of BatCoV PREDICT/PDF-2180, which is closely related to NeoCoV in all genome regions, cannot mediate entry to hDPP4-expressing cells [<xref rid="CIT0013" ref-type="bibr">13</xref>]. This further supported that NeoCoV and PREDICT/PDF-2180 are unlikely the immediate ancestors of MERS-CoV. On the other hand, Hp-BatCoV HKU25 and related viruses may represent close relatives to the immediate ancestor of MERS-CoV, based on its phylogenetic position in all genome regions including S protein.</p><p>The ability of Hp-BatCoV HKU25 to use hDPP4 for cell entry suggests that the S protein of related bat viruses may have evolved to cross the species barrier during the emergence of MERS-CoV. Using binding and pseudovirus assays, we demonstrated the ability of HKU25-S to bind to and use hDPP4 for cell entry,although with infection efficiency lower than that of MERS-S and HKU4-S. This is not only in line with the phylogenetic position of HKU25-S1 between HKU4-S1 (which can bind to hDPP4) and HKU5-S1 (which cannot), but it is also consistent with findings from structural modeling. Our results suggested that MERS-CoV may have originated from bat viruses having acquired a stepwise increasing ability to bind hDPP4 as they evolved. Previous molecular dating studies estimated that the time of divergence of MERS-CoVs was approximately 2010/2011 [<xref rid="CIT0040" ref-type="bibr">40–43</xref>]. The present dating results are in line with such estimation, with the tMRCA of MERS-CoVs dated to approximately 2009, and that of MERS-CoV, NeoCoV, Hp-BatCoV HKU25, and BtVs-BetaCoV/SC2013 dated to approximately 1939. Therefore, the immediate ancestor of MERS-CoV could well have emerged from bats in the last century through evolution in its S protein before jumping to camels and humans.</p><p>The evolutionary path of MERS-CoV may be different from that of SARS-CoV. For SARS-CoV, the overlapping habitat and geographical distribution of different horseshoe bats in China is believed to have fostered viral recombination leading to the epidemic. The SARS-CoV is most likely a recombinant virus arising from ancestral viruses in horseshoe bats before it jumped to civet and then humans [<xref rid="CIT0044" ref-type="bibr">44–47</xref>]. In contrast, there is currently no evidence to suggest that MERS-CoV is a recombinant virus. A previous study suggested that the genetically divergent S1 in NeoCoV may indicate intraspike recombination events involved in the emergence of MERS-CoV [<xref rid="CIT0011" ref-type="bibr">11</xref>]. As explained above, NeoCoV, rather than MERS-CoV, is more likely a recombinant virus. On the other hand, a stepwise evolution of the S protein in gaining the ability to use camel and human DPP4 may be an important mechanism for interspecies transmission during the emergence of MERS-CoV.</p></sec><sec id="s24"><title>CONCLUSIONS</title><p>Our results further support a possible bat origin of MERS-CoV and suggest that continuous surveillance of bats in the Middle East, Africa, and other regions may reveal the immediate animal origin of MERS-CoV. The application of similar state-of-the-art molecular studies on naturally evolving ancestral and intermediate viruses along the evolutionary path may provide further clues in understanding the mechanism of interspecies transmission of emerging viruses, while obviating the risks of generating dangerous mutants using the controversial, gain-of-function studies.</p></sec><sec sec-type="supplementary-material" id="s25"><title>Supplementary Data</title><p>Supplementary materials are available at <italic>The Journal of Infectious Diseases</italic> online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.</p><supplementary-material content-type="local-data" id="sup1"><label>Supplementary Table 1</label><media xlink:href="jiy018_suppl_supplementary_table_1.docx"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="sup2"><label>Supplementary Table 2</label><media xlink:href="jiy018_suppl_supplementary_table_2.docx"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="sup3"><label>Supplementary Table 3</label><media xlink:href="jiy018_suppl_supplementary_table_3.docx"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="sup4"><label>Supplementary Table 4</label><media xlink:href="jiy018_suppl_supplementary_table_4.docx"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="sup5"><label>Supplementary Table 5</label><media xlink:href="jiy018_suppl_supplementary_table_5.docx"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="sup6"><label>Supplementary Figure 1</label><media xlink:href="jiy018_suppl_supplementary_figure_1.png"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="sup7"><label>Supplementary Figure 2</label><media xlink:href="jiy018_suppl_supplementary_figure_2.png"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="sup8"><label>Supplementary Figure 3</label><media xlink:href="jiy018_suppl_supplementary_figure_3.png"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="sup9"><label>Supplementary Figure 4</label><media xlink:href="jiy018_suppl_supplementary_figure_4.png"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="sup10"><label>Supplementary Figure 5</label><media xlink:href="jiy018_suppl_supplementary_figure_5.jpeg"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="sup11"><label>Legends to Supporting Information</label><media xlink:href="jiy018_suppl_legends_to_supporting_information.docx"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material></sec></body><back><notes id="n1"><title>Notes</title><p><bold><italic>Financial support.</italic></bold> This work is partly funded by Theme-Based Research Scheme (T11-707/15-R) and Research Grant Council Grant, University Grant Council; Health and Medical Research Fund (13121102) of the Food and Health Bureau of Hong Kong Special Administrative Region (HKSAR); Croucher Senior Medical Research Fellowships, Committee for Research and Conference Grant, Strategic Research Theme Fund, University Development Fund and Special Research Achievement Award, The University of Hong Kong; Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Disease for the HKSAR Department of Health; National Science and Technology Major Project of China (grant number 2012ZX10004213); and GDAS Special Project of Science and Technology Development (2017GDASCX-0107).</p><p><bold><italic>Potential conflicts of interest.</italic></bold> All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.</p></notes><ref-list><title>References</title><ref id="CIT0001"><label>1.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Zaki</surname><given-names>AM</given-names></name>, <name name-style="western"><surname>van Boheemen</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Bestebroer</surname><given-names>TM</given-names></name>, <name name-style="western"><surname>Osterhaus</surname><given-names>AD</given-names></name>, <name name-style="western"><surname>Fouchier</surname><given-names>RA</given-names></name></person-group><article-title>Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia</article-title>. <source>N Engl J Med</source><year>2012</year>; <volume>367</volume>:<fpage>1814</fpage>–<lpage>20</lpage>.<pub-id pub-id-type="pmid">23075143</pub-id></mixed-citation></ref><ref id="CIT0002"><label>2.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>de Groot</surname><given-names>RJ</given-names></name>, <name name-style="western"><surname>Baker</surname><given-names>SC</given-names></name>, <name name-style="western"><surname>Baric</surname><given-names>RS</given-names></name><etal>et al</etal></person-group><article-title>Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group</article-title>. <source>J Virol</source><year>2013</year>; <volume>87</volume>:<fpage>7790</fpage>–<lpage>2</lpage>.<pub-id pub-id-type="pmid">23678167</pub-id></mixed-citation></ref><ref id="CIT0003"><label>3.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Raj</surname><given-names>VS</given-names></name>, <name name-style="western"><surname>Mou</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Smits</surname><given-names>SL</given-names></name><etal>et al</etal></person-group><article-title>Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC</article-title>. <source>Nature</source><year>2013</year>; <volume>495</volume>:<fpage>251</fpage>–<lpage>4</lpage>.<pub-id pub-id-type="pmid">23486063</pub-id></mixed-citation></ref><ref id="CIT0004"><label>4.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Reusken</surname><given-names>CB</given-names></name>, <name name-style="western"><surname>Haagmans</surname><given-names>BL</given-names></name>, <name name-style="western"><surname>Müller</surname><given-names>MA</given-names></name><etal>et al</etal></person-group><article-title>Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study</article-title>. <source>Lancet Infect Dis</source><year>2013</year>; <volume>13</volume>:<fpage>859</fpage>–<lpage>66</lpage>.<pub-id pub-id-type="pmid">23933067</pub-id></mixed-citation></ref><ref id="CIT0005"><label>5.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Haagmans</surname><given-names>BL</given-names></name>, <name name-style="western"><surname>Al Dhahiry</surname><given-names>SH</given-names></name>, <name name-style="western"><surname>Reusken</surname><given-names>CB</given-names></name><etal>et al</etal></person-group><article-title>Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation</article-title>. <source>Lancet Infect Dis</source><year>2014</year>; <volume>14</volume>:<fpage>140</fpage>–<lpage>5</lpage>.<pub-id pub-id-type="pmid">24355866</pub-id></mixed-citation></ref><ref id="CIT0006"><label>6.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Chan</surname><given-names>JF</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>To</surname><given-names>KK</given-names></name>, <name name-style="western"><surname>Cheng</surname><given-names>VC</given-names></name>, <name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Yuen</surname><given-names>KY</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease</article-title>. <source>Clin Microbiol Rev</source><year>2015</year>; <volume>28</volume>:<fpage>465</fpage>–<lpage>522</lpage>.<pub-id pub-id-type="pmid">25810418</pub-id></mixed-citation></ref><ref id="CIT0007"><label>7.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Wang</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name><etal>et al</etal></person-group><article-title>Comparative analysis of twelve genomes of three novel group 2c and group 2d coronaviruses reveals unique group and subgroup features</article-title>. <source>J Virol</source><year>2007</year>; <volume>81</volume>:<fpage>1574</fpage>–<lpage>85</lpage>.<pub-id pub-id-type="pmid">17121802</pub-id></mixed-citation></ref><ref id="CIT0008"><label>8.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>KS</given-names></name><etal>et al</etal></person-group><article-title>Molecular diversity of coronaviruses in bats</article-title>. <source>Virology</source><year>2006</year>; <volume>351</volume>:<fpage>180</fpage>–<lpage>7</lpage>.<pub-id pub-id-type="pmid">16647731</pub-id></mixed-citation></ref><ref id="CIT0009"><label>9.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>KS</given-names></name>, <name name-style="western"><surname>Tsang</surname><given-names>AK</given-names></name><etal>et al</etal></person-group><article-title>Genetic characterization of Betacoronavirus lineage C viruses in bats reveals marked sequence divergence in the spike protein of pipistrellus bat coronavirus HKU5 in Japanese pipistrelle: implications for the origin of the novel Middle East respiratory syndrome coronavirus</article-title>. <source>J Virol</source><year>2013</year>; <volume>87</volume>:<fpage>8638</fpage>–<lpage>50</lpage>.<pub-id pub-id-type="pmid">23720729</pub-id></mixed-citation></ref><ref id="CIT0010"><label>10.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>KS</given-names></name>, <name name-style="western"><surname>Tsang</surname><given-names>AK</given-names></name>, <name name-style="western"><surname>Yuen</surname><given-names>KY</given-names></name></person-group><article-title>Genetic relatedness of the novel human group C betacoronavirus to <italic>Tylonycteris</italic> bat coronavirus HKU4 and <italic>Pipistrellus</italic> bat coronavirus HKU5</article-title>. <source>Emerg Microbes Infect</source><year>2012</year>; <volume>1</volume>:<fpage>e35</fpage>.<pub-id pub-id-type="pmid">26038405</pub-id></mixed-citation></ref><ref id="CIT0011"><label>11.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Corman</surname><given-names>VM</given-names></name>, <name name-style="western"><surname>Ithete</surname><given-names>NL</given-names></name>, <name name-style="western"><surname>Richards</surname><given-names>LR</given-names></name><etal>et al</etal></person-group><article-title>Rooting the phylogenetic tree of Middle East respiratory syndrome coronavirus by characterization of a conspecific virus from an African bat</article-title>. <source>J Virol</source><year>2014</year>; <volume>88</volume>:<fpage>11297</fpage>–<lpage>303</lpage>.<pub-id pub-id-type="pmid">25031349</pub-id></mixed-citation></ref><ref id="CIT0012"><label>12.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yang</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Wu</surname><given-names>Z</given-names></name>, <name name-style="western"><surname>Ren</surname><given-names>X</given-names></name><etal>et al</etal></person-group><article-title>MERS-related betacoronavirus in <italic>Vespertilio superans</italic> bats, China</article-title>. <source>Emerg Infect Dis</source><year>2014</year>; <volume>20</volume>:<fpage>1260</fpage>–<lpage>2</lpage>.<pub-id pub-id-type="pmid">24960574</pub-id></mixed-citation></ref><ref id="CIT0013"><label>13.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Anthony</surname><given-names>SJ</given-names></name>, <name name-style="western"><surname>Gilardi</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Menachery</surname><given-names>VD</given-names></name><etal>et al</etal></person-group><article-title>Further evidence for bats as the evolutionary source of Middle East respiratory syndrome coronavirus</article-title>. <source>MBio</source><year>2017</year>; <volume>8</volume>:<fpage>pii</fpage>: <fpage>e00373</fpage>–<lpage>17</lpage>.</mixed-citation></ref><ref id="CIT0014"><label>14.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>van der Hoek</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Pyrc</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Jebbink</surname><given-names>MF</given-names></name><etal>et al</etal></person-group><article-title>Identification of a new human coronavirus</article-title>. <source>Nat Med</source><year>2004</year>; <volume>10</volume>:<fpage>368</fpage>–<lpage>73</lpage>.<pub-id pub-id-type="pmid">15034574</pub-id></mixed-citation></ref><ref id="CIT0015"><label>15.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Peiris</surname><given-names>JS</given-names></name>, <name name-style="western"><surname>Lai</surname><given-names>ST</given-names></name>, <name name-style="western"><surname>Poon</surname><given-names>LL</given-names></name><etal>et al</etal></person-group><article-title>Coronavirus as a possible cause of severe acute respiratory syndrome</article-title>. <source>Lancet</source><year>2003</year>; <volume>361</volume>:<fpage>1319</fpage>–<lpage>25</lpage>.<pub-id pub-id-type="pmid">12711465</pub-id></mixed-citation></ref><ref id="CIT0016"><label>16.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Chu</surname><given-names>CM</given-names></name><etal>et al</etal></person-group><article-title>Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia</article-title>. <source>J Virol</source><year>2005</year>; <volume>79</volume>:<fpage>884</fpage>–<lpage>95</lpage>.<pub-id pub-id-type="pmid">15613317</pub-id></mixed-citation></ref><ref id="CIT0017"><label>17.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Lam</surname><given-names>CS</given-names></name><etal>et al</etal></person-group><article-title>Discovery of seven novel mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus</article-title>. <source>J Virol</source><year>2012</year>; <volume>86</volume>:<fpage>3995</fpage>–<lpage>4008</lpage>.<pub-id pub-id-type="pmid">22278237</pub-id></mixed-citation></ref><ref id="CIT0018"><label>18.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>KS</given-names></name><etal>et al</etal></person-group><article-title>Discovery of a novel coronavirus, China <italic>Rattus</italic> coronavirus HKU24, from Norway rats supports the murine origin of <italic>Betacoronavirus</italic> 1 and has implications for the ancestor of <italic>Betacoronavirus</italic> lineage A</article-title>. <source>J Virol</source><year>2014</year>; <volume>89</volume>:<fpage>3076</fpage>–<lpage>92</lpage>.<pub-id pub-id-type="pmid">25552712</pub-id></mixed-citation></ref><ref id="CIT0019"><label>19.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lai</surname><given-names>MM</given-names></name>, <name name-style="western"><surname>Cavanagh</surname><given-names>D</given-names></name></person-group><article-title>The molecular biology of coronaviruses</article-title>. <source>Adv Virus Res</source><year>1997</year>; <volume>48</volume>:<fpage>1</fpage>–<lpage>100</lpage>.<pub-id pub-id-type="pmid">9233431</pub-id></mixed-citation></ref><ref id="CIT0020"><label>20.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Brian</surname><given-names>DA</given-names></name>, <name name-style="western"><surname>Baric</surname><given-names>RS</given-names></name></person-group><article-title>Coronavirus genome structure and replication</article-title>. <source>Curr Top Microbiol Immunol</source><year>2005</year>; <volume>287</volume>:<fpage>1</fpage>–<lpage>30</lpage>.<pub-id pub-id-type="pmid">15609507</pub-id></mixed-citation></ref><ref id="CIT0021"><label>21.</label><mixed-citation publication-type="confproc"><person-group person-group-type="author"><name name-style="western"><surname>de Groot</surname><given-names>RJ</given-names></name>, <name name-style="western"><surname>Baker</surname><given-names>SC</given-names></name>, <name name-style="western"><surname>Baric</surname><given-names>R</given-names></name><etal>et al</etal></person-group><article-title>Coronaviridae</article-title>. In: <source>Virus Taxonomy, Classification and Nomenclature of Viruses</source>. <conf-name>Ninth Report of the International Committee on Taxonomy of Viruses</conf-name>, <publisher-name>International Union of Microbiological Societies, Virology Division</publisher-name>; <year>2011</year>: pp <fpage>806</fpage>–<lpage>28</lpage>.</mixed-citation></ref><ref id="CIT0022"><label>22.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>van Boheemen</surname><given-names>S</given-names></name>, <name name-style="western"><surname>de Graaf</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Lauber</surname><given-names>C</given-names></name><etal>et al</etal></person-group><article-title>Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans</article-title>. <source>MBio</source><year>2012</year>; <volume>3</volume>:<fpage>pii</fpage>: <fpage>e00473</fpage>–<lpage>12</lpage>.</mixed-citation></ref><ref id="CIT0023"><label>23.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Wang</surname><given-names>Q</given-names></name>, <name name-style="western"><surname>Qi</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Yuan</surname><given-names>Y</given-names></name><etal>et al</etal></person-group><article-title>Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26</article-title>. <source>Cell Host Microbe</source><year>2014</year>; <volume>16</volume>:<fpage>328</fpage>–<lpage>37</lpage>.<pub-id pub-id-type="pmid">25211075</pub-id></mixed-citation></ref><ref id="CIT0024"><label>24.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Agnarsson</surname><given-names>I</given-names></name>, <name name-style="western"><surname>Zambrana-Torrelio</surname><given-names>CM</given-names></name>, <name name-style="western"><surname>Flores-Saldana</surname><given-names>NP</given-names></name>, <name name-style="western"><surname>May-Collado</surname><given-names>LJ</given-names></name></person-group><article-title>A time-calibrated species-level phylogeny of bats (Chiroptera, Mammalia)</article-title>. <source>PLoS Curr</source><year>2011</year>; <volume>3</volume>:<fpage>RRN1212</fpage>.<pub-id pub-id-type="pmid">21327164</pub-id></mixed-citation></ref><ref id="CIT0025"><label>25.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Caì</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Yú</surname><given-names>SQ</given-names></name>, <name name-style="western"><surname>Postnikova</surname><given-names>EN</given-names></name><etal>et al</etal></person-group><article-title>CD26/DPP4 cell-surface expression in bat cells correlates with bat cell susceptibility to Middle East respiratory syndrome coronavirus (MERS-CoV) infection and evolution of persistent infection</article-title>. <source>PLoS One</source><year>2014</year>; <volume>9</volume>:<fpage>e112060</fpage>.<pub-id pub-id-type="pmid">25409519</pub-id></mixed-citation></ref><ref id="CIT0026"><label>26.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Munster</surname><given-names>VJ</given-names></name>, <name name-style="western"><surname>Adney</surname><given-names>DR</given-names></name>, <name name-style="western"><surname>van Doremalen</surname><given-names>N</given-names></name><etal>et al</etal></person-group><article-title>Replication and shedding of MERS-CoV in Jamaican fruit bats (<italic>Artibeus jamaicensis</italic>)</article-title>. <source>Sci Rep</source><year>2016</year>; <volume>6</volume>:<fpage>21878</fpage>.<pub-id pub-id-type="pmid">26899616</pub-id></mixed-citation></ref><ref id="CIT0027"><label>27.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>KS</given-names></name><etal>et al</etal></person-group><article-title>Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats</article-title>. <source>Proc Natl Acad Sci U S A</source><year>2005</year>; <volume>102</volume>:<fpage>14040</fpage>–<lpage>5</lpage>.<pub-id pub-id-type="pmid">16169905</pub-id></mixed-citation></ref><ref id="CIT0028"><label>28.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yob</surname><given-names>JM</given-names></name>, <name name-style="western"><surname>Field</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Rashdi</surname><given-names>AM</given-names></name><etal>et al</etal></person-group><article-title>Nipah virus infection in bats (order Chiroptera) in peninsular Malaysia</article-title>. <source>Emerg Infect Dis</source><year>2001</year>; <volume>7</volume>:<fpage>439</fpage>–<lpage>41</lpage>.<pub-id pub-id-type="pmid">11384522</pub-id></mixed-citation></ref><ref id="CIT0029"><label>29.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Yip</surname><given-names>CC</given-names></name><etal>et al</etal></person-group><article-title>Isolation and characterization of a novel betacoronavirus subgroup A coronavirus, rabbit coronavirus HKU14, from domestic rabbits</article-title>. <source>J Virol</source><year>2012</year>; <volume>86</volume>:<fpage>5481</fpage>–<lpage>96</lpage>.<pub-id pub-id-type="pmid">22398294</pub-id></mixed-citation></ref><ref id="CIT0030"><label>30.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Huang</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Woo</surname><given-names>PC</given-names></name>, <name name-style="western"><surname>Yuen</surname><given-names>KY</given-names></name></person-group><article-title>CoVDB: a comprehensive database for comparative analysis of coronavirus genes and genomes</article-title>. <source>Nucleic Acids Res</source><year>2008</year>; <volume>36</volume>: <fpage>D504</fpage>–<lpage>11</lpage>.<pub-id pub-id-type="pmid">17913743</pub-id></mixed-citation></ref><ref id="CIT0031"><label>31.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Wernery</surname><given-names>R</given-names></name>, <name name-style="western"><surname>Wong</surname><given-names>EY</given-names></name><etal>et al</etal></person-group><article-title>Polyphyletic origin of MERS coronaviruses and isolation of a novel clade A strain from dromedary camels in the United Arab Emirates</article-title>. <source>Emerg Microbes Infect</source><year>2016</year>; <volume>5</volume>:<fpage>e128</fpage>.<pub-id pub-id-type="pmid">27999424</pub-id></mixed-citation></ref><ref id="CIT0032"><label>32.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Huang</surname><given-names>X</given-names></name>, <name name-style="western"><surname>Dong</surname><given-names>W</given-names></name>, <name name-style="western"><surname>Milewska</surname><given-names>A</given-names></name><etal>et al</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>13</lpage>.<pub-id pub-id-type="pmid">25926653</pub-id></mixed-citation></ref><ref id="CIT0033"><label>33.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Sun</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Qi</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Liu</surname><given-names>C</given-names></name><etal>et al</etal></person-group><article-title>Nonmuscle myosin heavy chain IIA is a critical factor contributing to the efficiency of early infection of severe fever with thrombocytopenia syndrome virus</article-title>. <source>J Virol</source><year>2014</year>; <volume>88</volume>:<fpage>237</fpage>–<lpage>48</lpage>.<pub-id pub-id-type="pmid">24155382</pub-id></mixed-citation></ref><ref id="CIT0034"><label>34.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Xiong</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Yang</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Ye</surname><given-names>YN</given-names></name><etal>et al</etal></person-group><article-title><italic>Laribacter hongkongensis</italic> anaerobic adaptation mediated by arginine metabolism is controlled by the cooperation of FNR and ArgR</article-title>. <source>Environ Microbiol</source><year>2017</year>; <volume>19</volume>:<fpage>1266</fpage>–<lpage>80</lpage>.<pub-id pub-id-type="pmid">28028888</pub-id></mixed-citation></ref><ref id="CIT0035"><label>35.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lu</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Hu</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Wang</surname><given-names>Q</given-names></name><etal>et al</etal></person-group><article-title>Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26</article-title>. <source>Nature</source><year>2013</year>; <volume>500</volume>:<fpage>227</fpage>–<lpage>31</lpage>.<pub-id pub-id-type="pmid">23831647</pub-id></mixed-citation></ref><ref id="CIT0036"><label>36.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yang</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Du</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Liu</surname><given-names>C</given-names></name><etal>et al</etal></person-group><article-title>Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus</article-title>. <source>Proc Natl Acad Sci U S A</source><year>2014</year>; <volume>111</volume>:<fpage>12516</fpage>–<lpage>21</lpage>.<pub-id pub-id-type="pmid">25114257</pub-id></mixed-citation></ref><ref id="CIT0037"><label>37.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Wang</surname><given-names>N</given-names></name>, <name name-style="western"><surname>Shi</surname><given-names>X</given-names></name>, <name name-style="western"><surname>Jiang</surname><given-names>L</given-names></name><etal>et al</etal></person-group><article-title>Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4</article-title>. <source>Cell Res</source><year>2013</year>; <volume>23</volume>:<fpage>986</fpage>–<lpage>93</lpage>.<pub-id pub-id-type="pmid">23835475</pub-id></mixed-citation></ref><ref id="CIT0038"><label>38.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Niemeyer</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Zillinger</surname><given-names>T</given-names></name>, <name name-style="western"><surname>Muth</surname><given-names>D</given-names></name><etal>et al</etal></person-group><article-title>Middle East respiratory syndrome coronavirus accessory protein 4a is a type I interferon antagonist</article-title>. <source>J Virol</source><year>2013</year>; <volume>87</volume>:<fpage>12489</fpage>–<lpage>95</lpage>.<pub-id pub-id-type="pmid">24027320</pub-id></mixed-citation></ref><ref id="CIT0039"><label>39.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Thornbrough</surname><given-names>JM</given-names></name>, <name name-style="western"><surname>Jha</surname><given-names>BK</given-names></name>, <name name-style="western"><surname>Yount</surname><given-names>B</given-names></name><etal>et al</etal></person-group><article-title>Middle East respiratory syndrome coronavirus NS4b protein inhibits host RNase L activation</article-title>. <source>MBio</source><year>2016</year>; <volume>7</volume>:<fpage>e00258</fpage>.<pub-id pub-id-type="pmid">27025250</pub-id></mixed-citation></ref><ref id="CIT0040"><label>40.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Cotten</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Watson</surname><given-names>SJ</given-names></name>, <name name-style="western"><surname>Zumla</surname><given-names>AI</given-names></name><etal>et al</etal></person-group><article-title>Spread, circulation, and evolution of the middle East respiratory syndrome coronavirus</article-title>. <source>MBio</source><year>2014</year>; <volume>5</volume>:<fpage>pii</fpage>: <fpage>e01062</fpage>–<lpage>13</lpage>.</mixed-citation></ref><ref id="CIT0041"><label>41.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Sabir</surname><given-names>JS</given-names></name>, <name name-style="western"><surname>Lam</surname><given-names>TT</given-names></name>, <name name-style="western"><surname>Ahmed</surname><given-names>MM</given-names></name><etal>et al</etal></person-group><article-title>Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia</article-title>. <source>Science</source><year>2016</year>; <volume>351</volume>:<fpage>81</fpage>–<lpage>4</lpage>.<pub-id pub-id-type="pmid">26678874</pub-id></mixed-citation></ref><ref id="CIT0042"><label>42.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Cauchemez</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Fraser</surname><given-names>C</given-names></name>, <name name-style="western"><surname>Van Kerkhove</surname><given-names>MD</given-names></name><etal>et al</etal></person-group><article-title>Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility</article-title>. <source>Lancet Infect Dis</source><year>2014</year>; <volume>14</volume>:<fpage>50</fpage>–<lpage>6</lpage>.<pub-id pub-id-type="pmid">24239323</pub-id></mixed-citation></ref><ref id="CIT0043"><label>43.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Drosten</surname><given-names>C</given-names></name>, <name name-style="western"><surname>Seilmaier</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Corman</surname><given-names>VM</given-names></name><etal>et al</etal></person-group><article-title>Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection</article-title>. <source>Lancet Infect Dis</source><year>2013</year>; <volume>13</volume>:<fpage>745</fpage>–<lpage>51</lpage>.<pub-id pub-id-type="pmid">23782859</pub-id></mixed-citation></ref><ref id="CIT0044"><label>44.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Li</surname><given-names>KS</given-names></name>, <name name-style="western"><surname>Huang</surname><given-names>Y</given-names></name><etal>et al</etal></person-group><article-title>Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related rhinolophus bat coronavirus in china reveal bats as a reservoir for acute, self-limiting infection that allows recombination events</article-title>. <source>J Virol</source><year>2010</year>; <volume>84</volume>:<fpage>2808</fpage>–<lpage>19</lpage>.<pub-id pub-id-type="pmid">20071579</pub-id></mixed-citation></ref><ref id="CIT0045"><label>45.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Hon</surname><given-names>CC</given-names></name>, <name name-style="western"><surname>Lam</surname><given-names>TY</given-names></name>, <name name-style="western"><surname>Shi</surname><given-names>ZL</given-names></name><etal>et al</etal></person-group><article-title>Evidence of the recombinant origin of a bat severe acute respiratory syndrome (SARS)-like coronavirus and its implications on the direct ancestor of SARS coronavirus</article-title>. <source>J Virol</source><year>2008</year>; <volume>82</volume>:<fpage>1819</fpage>–<lpage>26</lpage>.<pub-id pub-id-type="pmid">18057240</pub-id></mixed-citation></ref><ref id="CIT0046"><label>46.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lau</surname><given-names>SK</given-names></name>, <name name-style="western"><surname>Feng</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Chen</surname><given-names>H</given-names></name><etal>et al</etal></person-group><article-title>Severe acute respiratory syndrome (SARS) coronavirus ORF8 protein is acquired from SARS-related coronavirus from greater horseshoe bats through recombination</article-title>. <source>J Virol</source><year>2015</year>; <volume>89</volume>:<fpage>10532</fpage>–<lpage>47</lpage>.<pub-id pub-id-type="pmid">26269185</pub-id></mixed-citation></ref><ref id="CIT0047"><label>47.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Song</surname><given-names>HD</given-names></name>, <name name-style="western"><surname>Tu</surname><given-names>CC</given-names></name>, <name name-style="western"><surname>Zhang</surname><given-names>GW</given-names></name><etal>et al</etal></person-group><article-title>Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human</article-title>. <source>Proc Natl Acad Sci U S A</source><year>2005</year>; <volume>102</volume>:<fpage>2430</fpage>–<lpage>5</lpage>.<pub-id pub-id-type="pmid">15695582</pub-id></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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