The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases
Identifieur interne : 001105 ( Pmc/Curation ); précédent : 001104; suivant : 001106The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases
Auteurs : James T. Earnest [États-Unis] ; Michael P. Hantak [États-Unis] ; Kun Li [États-Unis] ; Paul B. Mccray [États-Unis] ; Stanley Perlman [États-Unis] ; Tom Gallagher [États-Unis]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2017.
Abstract
Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease. This CD9-facilitated condensation of receptors and proteases allowed MERS-CoV pseudoviruses to enter cells rapidly and efficiently. Without CD9, MERS-CoV viruses were not activated by TTSPs, and they trafficked into endosomes to be cleaved much later and less efficiently by cathepsins. Thus, we identified DPP4:CD9:TTSP as the protein complexes necessary for early, efficient MERS-CoV entry. To evaluate the importance of these complexes in an
Url:
DOI: 10.1371/journal.ppat.1006546
PubMed: 28759649
PubMed Central: 5552337
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :001105
Links to Exploration step
PMC:5552337Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases</title>
<author><name sortKey="Earnest, James T" sort="Earnest, James T" uniqKey="Earnest J" first="James T." last="Earnest">James T. Earnest</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hantak, Michael P" sort="Hantak, Michael P" uniqKey="Hantak M" first="Michael P." last="Hantak">Michael P. Hantak</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Li, Kun" sort="Li, Kun" uniqKey="Li K" first="Kun" last="Li">Kun Li</name>
<affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mccray, Paul B" sort="Mccray, Paul B" uniqKey="Mccray P" first="Paul B." last="Mccray">Paul B. Mccray</name>
<affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
<affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Microbiology, University of Iowa, Iowa City, IA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology, University of Iowa, Iowa City, IA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gallagher, Tom" sort="Gallagher, Tom" uniqKey="Gallagher T" first="Tom" last="Gallagher">Tom Gallagher</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">28759649</idno>
<idno type="pmc">5552337</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552337</idno>
<idno type="RBID">PMC:5552337</idno>
<idno type="doi">10.1371/journal.ppat.1006546</idno>
<date when="2017">2017</date>
<idno type="wicri:Area/Pmc/Corpus">001105</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001105</idno>
<idno type="wicri:Area/Pmc/Curation">001105</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001105</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases</title>
<author><name sortKey="Earnest, James T" sort="Earnest, James T" uniqKey="Earnest J" first="James T." last="Earnest">James T. Earnest</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hantak, Michael P" sort="Hantak, Michael P" uniqKey="Hantak M" first="Michael P." last="Hantak">Michael P. Hantak</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Li, Kun" sort="Li, Kun" uniqKey="Li K" first="Kun" last="Li">Kun Li</name>
<affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mccray, Paul B" sort="Mccray, Paul B" uniqKey="Mccray P" first="Paul B." last="Mccray">Paul B. Mccray</name>
<affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
<affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Microbiology, University of Iowa, Iowa City, IA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology, University of Iowa, Iowa City, IA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gallagher, Tom" sort="Gallagher, Tom" uniqKey="Gallagher T" first="Tom" last="Gallagher">Tom Gallagher</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS Pathogens</title>
<idno type="ISSN">1553-7366</idno>
<idno type="eISSN">1553-7374</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease. This CD9-facilitated condensation of receptors and proteases allowed MERS-CoV pseudoviruses to enter cells rapidly and efficiently. Without CD9, MERS-CoV viruses were not activated by TTSPs, and they trafficked into endosomes to be cleaved much later and less efficiently by cathepsins. Thus, we identified DPP4:CD9:TTSP as the protein complexes necessary for early, efficient MERS-CoV entry. To evaluate the importance of these complexes in an <italic>in vivo</italic>
CoV infection model, we used recombinant Adenovirus 5 (rAd5) vectors to express human DPP4 in mouse lungs, thereby sensitizing the animals to MERS-CoV infection. When the rAd5-hDPP4 vectors co-expressed small RNAs silencing <italic>Cd9</italic>
or <italic>Tmprss2</italic>
, the animals were significantly less susceptible, indicating that CD9 and TMPRSS2 facilitated robust <italic>in vivo</italic>
MERS-CoV infection of mouse lungs. Furthermore, the S proteins of virulent mouse-adapted MERS-CoVs acquired a CD9-dependent cell entry character, suggesting that CD9 is a selective agent in the evolution of CoV virulence.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bottcher Friebertshauser, E" uniqKey="Bottcher Friebertshauser E">E Bottcher-Friebertshauser</name>
</author>
<author><name sortKey="Freuer, C" uniqKey="Freuer C">C Freuer</name>
</author>
<author><name sortKey="Sielaff, F" uniqKey="Sielaff F">F Sielaff</name>
</author>
<author><name sortKey="Schmidt, S" uniqKey="Schmidt S">S Schmidt</name>
</author>
<author><name sortKey="Eickmann, M" uniqKey="Eickmann M">M Eickmann</name>
</author>
<author><name sortKey="Uhlendorff, J" uniqKey="Uhlendorff J">J Uhlendorff</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mothes, W" uniqKey="Mothes W">W Mothes</name>
</author>
<author><name sortKey="Boerger, Al" uniqKey="Boerger A">AL Boerger</name>
</author>
<author><name sortKey="Narayan, S" uniqKey="Narayan S">S Narayan</name>
</author>
<author><name sortKey="Cunningham, Jm" uniqKey="Cunningham J">JM Cunningham</name>
</author>
<author><name sortKey="Young, Jat" uniqKey="Young J">JAT Young</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S Matsuyama</name>
</author>
<author><name sortKey="Taguchi, F" uniqKey="Taguchi F">F Taguchi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dveksler, Gs" uniqKey="Dveksler G">GS Dveksler</name>
</author>
<author><name sortKey="Pensiero, Mn" uniqKey="Pensiero M">MN Pensiero</name>
</author>
<author><name sortKey="Cardellichio, Cb" uniqKey="Cardellichio C">CB Cardellichio</name>
</author>
<author><name sortKey="Williams, Rk" uniqKey="Williams R">RK Williams</name>
</author>
<author><name sortKey="Jiang, Gs" uniqKey="Jiang G">GS Jiang</name>
</author>
<author><name sortKey="Holmes, Kv" uniqKey="Holmes K">KV Holmes</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Li, W" uniqKey="Li W">W Li</name>
</author>
<author><name sortKey="Moore, Mj" uniqKey="Moore M">MJ Moore</name>
</author>
<author><name sortKey="Vasilieva, N" uniqKey="Vasilieva N">N Vasilieva</name>
</author>
<author><name sortKey="Sui, J" uniqKey="Sui J">J Sui</name>
</author>
<author><name sortKey="Wong, Sk" uniqKey="Wong S">SK Wong</name>
</author>
<author><name sortKey="Berne, Ma" uniqKey="Berne M">MA Berne</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yeager, Cl" uniqKey="Yeager C">CL Yeager</name>
</author>
<author><name sortKey="Ashmun, Ra" uniqKey="Ashmun R">RA Ashmun</name>
</author>
<author><name sortKey="Williams, Rk" uniqKey="Williams R">RK Williams</name>
</author>
<author><name sortKey="Cardellichio, Cb" uniqKey="Cardellichio C">CB Cardellichio</name>
</author>
<author><name sortKey="Shapiro, Lh" uniqKey="Shapiro L">LH Shapiro</name>
</author>
<author><name sortKey="Look, At" uniqKey="Look A">AT Look</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>
<author><name sortKey="Dekkers, Dh" uniqKey="Dekkers D">DH Dekkers</name>
</author>
<author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</name>
</author>
<author><name sortKey="Dijkman, R" uniqKey="Dijkman R">R Dijkman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bertram, S" uniqKey="Bertram S">S Bertram</name>
</author>
<author><name sortKey="Dijkman, R" uniqKey="Dijkman R">R Dijkman</name>
</author>
<author><name sortKey="Habjan, M" uniqKey="Habjan M">M Habjan</name>
</author>
<author><name sortKey="Heurich, A" uniqKey="Heurich A">A Heurich</name>
</author>
<author><name sortKey="Gierer, S" uniqKey="Gierer S">S Gierer</name>
</author>
<author><name sortKey="Glowacka, I" uniqKey="Glowacka I">I Glowacka</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gierer, S" uniqKey="Gierer S">S Gierer</name>
</author>
<author><name sortKey="Bertram, S" uniqKey="Bertram S">S Bertram</name>
</author>
<author><name sortKey="Kaup, F" uniqKey="Kaup F">F Kaup</name>
</author>
<author><name sortKey="Wrensch, F" uniqKey="Wrensch F">F Wrensch</name>
</author>
<author><name sortKey="Heurich, A" uniqKey="Heurich A">A Heurich</name>
</author>
<author><name sortKey="Kramer Kuhl, A" uniqKey="Kramer Kuhl A">A Kramer-Kuhl</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Glowacka, I" uniqKey="Glowacka I">I Glowacka</name>
</author>
<author><name sortKey="Bertram, S" uniqKey="Bertram S">S Bertram</name>
</author>
<author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</name>
</author>
<author><name sortKey="Allen, P" uniqKey="Allen P">P Allen</name>
</author>
<author><name sortKey="Soilleux, E" uniqKey="Soilleux E">E Soilleux</name>
</author>
<author><name sortKey="Pfefferle, S" uniqKey="Pfefferle S">S Pfefferle</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bertram, S" uniqKey="Bertram S">S Bertram</name>
</author>
<author><name sortKey="Glowacka, I" uniqKey="Glowacka I">I Glowacka</name>
</author>
<author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Müller</name>
</author>
<author><name sortKey="Lavender, H" uniqKey="Lavender H">H Lavender</name>
</author>
<author><name sortKey="Gnirss, K" uniqKey="Gnirss K">K Gnirss</name>
</author>
<author><name sortKey="Nehlmeier, I" uniqKey="Nehlmeier I">I Nehlmeier</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Magnus, C" uniqKey="Magnus C">C Magnus</name>
</author>
<author><name sortKey="Rusert, P" uniqKey="Rusert P">P Rusert</name>
</author>
<author><name sortKey="Bonhoeffer, S" uniqKey="Bonhoeffer S">S Bonhoeffer</name>
</author>
<author><name sortKey="Trkola, A" uniqKey="Trkola A">A Trkola</name>
</author>
<author><name sortKey="Regoes, Rr" uniqKey="Regoes R">RR Regoes</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ivanovic, T" uniqKey="Ivanovic T">T Ivanovic</name>
</author>
<author><name sortKey="Choi, Jl" uniqKey="Choi J">JL Choi</name>
</author>
<author><name sortKey="Whelan, Sp" uniqKey="Whelan S">SP Whelan</name>
</author>
<author><name sortKey="Van Oijen, Am" uniqKey="Van Oijen A">AM van Oijen</name>
</author>
<author><name sortKey="Harrison, Sc" uniqKey="Harrison S">SC Harrison</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Earnest, Jt" uniqKey="Earnest J">JT Earnest</name>
</author>
<author><name sortKey="Hantak, Mp" uniqKey="Hantak M">MP Hantak</name>
</author>
<author><name sortKey="Park, Je" uniqKey="Park J">JE Park</name>
</author>
<author><name sortKey="Gallagher, T" uniqKey="Gallagher T">T Gallagher</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Charrin, S" uniqKey="Charrin S">S Charrin</name>
</author>
<author><name sortKey="Le Naour, F" uniqKey="Le Naour F">F le Naour</name>
</author>
<author><name sortKey="Silvie, O" uniqKey="Silvie O">O Silvie</name>
</author>
<author><name sortKey="Milhiet, Pe" uniqKey="Milhiet P">PE Milhiet</name>
</author>
<author><name sortKey="Boucheix, C" uniqKey="Boucheix C">C Boucheix</name>
</author>
<author><name sortKey="Rubinstein, E" uniqKey="Rubinstein E">E Rubinstein</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stipp, Cs" uniqKey="Stipp C">CS Stipp</name>
</author>
<author><name sortKey="Kolesnikova, Tv" uniqKey="Kolesnikova T">TV Kolesnikova</name>
</author>
<author><name sortKey="Hemler, Me" uniqKey="Hemler M">ME Hemler</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sala Valdes, M" uniqKey="Sala Valdes M">M Sala-Valdes</name>
</author>
<author><name sortKey="Ursa, A" uniqKey="Ursa A">A Ursa</name>
</author>
<author><name sortKey="Charrin, S" uniqKey="Charrin S">S Charrin</name>
</author>
<author><name sortKey="Rubinstein, E" uniqKey="Rubinstein E">E Rubinstein</name>
</author>
<author><name sortKey="Hemler, Me" uniqKey="Hemler M">ME Hemler</name>
</author>
<author><name sortKey="Sanchez Madrid, F" uniqKey="Sanchez Madrid F">F Sanchez-Madrid</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yauch, Rl" uniqKey="Yauch R">RL Yauch</name>
</author>
<author><name sortKey="Kazarov, Ar" uniqKey="Kazarov A">AR Kazarov</name>
</author>
<author><name sortKey="Desai, B" uniqKey="Desai B">B Desai</name>
</author>
<author><name sortKey="Lee, Rt" uniqKey="Lee R">RT Lee</name>
</author>
<author><name sortKey="Hemler, Me" uniqKey="Hemler M">ME Hemler</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yanez Mo, M" uniqKey="Yanez Mo M">M Yanez-Mo</name>
</author>
<author><name sortKey="Gutierrez Lopez, Md" uniqKey="Gutierrez Lopez M">MD Gutierrez-Lopez</name>
</author>
<author><name sortKey="Cabanas, C" uniqKey="Cabanas C">C Cabanas</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gutierrez Lopez, Md" uniqKey="Gutierrez Lopez M">MD Gutierrez-Lopez</name>
</author>
<author><name sortKey="Gilsanz, A" uniqKey="Gilsanz A">A Gilsanz</name>
</author>
<author><name sortKey="Yanez Mo, M" uniqKey="Yanez Mo M">M Yanez-Mo</name>
</author>
<author><name sortKey="Ovalle, S" uniqKey="Ovalle S">S Ovalle</name>
</author>
<author><name sortKey="Lafuente, Em" uniqKey="Lafuente E">EM Lafuente</name>
</author>
<author><name sortKey="Dominguez, C" uniqKey="Dominguez C">C Dominguez</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Andre, M" uniqKey="Andre M">M Andre</name>
</author>
<author><name sortKey="Le Caer, Jp" uniqKey="Le Caer J">JP Le Caer</name>
</author>
<author><name sortKey="Greco, C" uniqKey="Greco C">C Greco</name>
</author>
<author><name sortKey="Planchon, S" uniqKey="Planchon S">S Planchon</name>
</author>
<author><name sortKey="El Nemer, W" uniqKey="El Nemer W">W El Nemer</name>
</author>
<author><name sortKey="Boucheix, C" uniqKey="Boucheix C">C Boucheix</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Okamoto, T" uniqKey="Okamoto T">T Okamoto</name>
</author>
<author><name sortKey="Iwata, S" uniqKey="Iwata S">S Iwata</name>
</author>
<author><name sortKey="Yamazaki, H" uniqKey="Yamazaki H">H Yamazaki</name>
</author>
<author><name sortKey="Hatano, R" uniqKey="Hatano R">R Hatano</name>
</author>
<author><name sortKey="Komiya, E" uniqKey="Komiya E">E Komiya</name>
</author>
<author><name sortKey="Dang, Nh" uniqKey="Dang N">NH Dang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zoller, M" uniqKey="Zoller M">M Zoller</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bugge, Th" uniqKey="Bugge T">TH Bugge</name>
</author>
<author><name sortKey="Antalis, Tm" uniqKey="Antalis T">TM Antalis</name>
</author>
<author><name sortKey="Wu, Q" uniqKey="Wu Q">Q Wu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shirato, K" uniqKey="Shirato K">K Shirato</name>
</author>
<author><name sortKey="Kawase, M" uniqKey="Kawase M">M Kawase</name>
</author>
<author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S Matsuyama</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name>
</author>
<author><name sortKey="Li, K" uniqKey="Li K">K Li</name>
</author>
<author><name sortKey="Wohlford Lenane, C" uniqKey="Wohlford Lenane C">C Wohlford-Lenane</name>
</author>
<author><name sortKey="Agnihothram, Ss" uniqKey="Agnihothram S">SS Agnihothram</name>
</author>
<author><name sortKey="Fett, C" uniqKey="Fett C">C Fett</name>
</author>
<author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Montpellier, C" uniqKey="Montpellier C">C Montpellier</name>
</author>
<author><name sortKey="Tews, Ba" uniqKey="Tews B">BA Tews</name>
</author>
<author><name sortKey="Poitrimole, J" uniqKey="Poitrimole J">J Poitrimole</name>
</author>
<author><name sortKey="Rocha Perugini, V" uniqKey="Rocha Perugini V">V Rocha-Perugini</name>
</author>
<author><name sortKey="D Arienzo, V" uniqKey="D Arienzo V">V D'Arienzo</name>
</author>
<author><name sortKey="Potel, J" uniqKey="Potel J">J Potel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="He, J" uniqKey="He J">J He</name>
</author>
<author><name sortKey="Sun, E" uniqKey="Sun E">E Sun</name>
</author>
<author><name sortKey="Bujny, Mv" uniqKey="Bujny M">MV Bujny</name>
</author>
<author><name sortKey="Kim, D" uniqKey="Kim D">D Kim</name>
</author>
<author><name sortKey="Davidson, Mw" uniqKey="Davidson M">MW Davidson</name>
</author>
<author><name sortKey="Zhuang, X" uniqKey="Zhuang X">X Zhuang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ran, Fa" uniqKey="Ran F">FA Ran</name>
</author>
<author><name sortKey="Hsu, Pd" uniqKey="Hsu P">PD Hsu</name>
</author>
<author><name sortKey="Wright, J" uniqKey="Wright J">J Wright</name>
</author>
<author><name sortKey="Agarwala, V" uniqKey="Agarwala V">V Agarwala</name>
</author>
<author><name sortKey="Scott, Da" uniqKey="Scott D">DA Scott</name>
</author>
<author><name sortKey="Zhang, F" uniqKey="Zhang F">F Zhang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hemler, Me" uniqKey="Hemler M">ME Hemler</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Claas, C" uniqKey="Claas C">C Claas</name>
</author>
<author><name sortKey="Stipp, Cs" uniqKey="Stipp C">CS Stipp</name>
</author>
<author><name sortKey="Hemler, Me" uniqKey="Hemler M">ME Hemler</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Soderberg, O" uniqKey="Soderberg O">O Soderberg</name>
</author>
<author><name sortKey="Gullberg, M" uniqKey="Gullberg M">M Gullberg</name>
</author>
<author><name sortKey="Jarvius, M" uniqKey="Jarvius M">M Jarvius</name>
</author>
<author><name sortKey="Ridderstrale, K" uniqKey="Ridderstrale K">K Ridderstrale</name>
</author>
<author><name sortKey="Leuchowius, K J" uniqKey="Leuchowius K">K-J Leuchowius</name>
</author>
<author><name sortKey="Jarvius, J" uniqKey="Jarvius J">J Jarvius</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhou, H" uniqKey="Zhou H">H Zhou</name>
</author>
<author><name sortKey="Bouwman, K" uniqKey="Bouwman K">K Bouwman</name>
</author>
<author><name sortKey="Schotanus, M" uniqKey="Schotanus M">M Schotanus</name>
</author>
<author><name sortKey="Verweij, C" uniqKey="Verweij C">C Verweij</name>
</author>
<author><name sortKey="Marrero, Ja" uniqKey="Marrero J">JA Marrero</name>
</author>
<author><name sortKey="Dillon, D" uniqKey="Dillon D">D Dillon</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Grigorov, B" uniqKey="Grigorov B">B Grigorov</name>
</author>
<author><name sortKey="Reungoat, E" uniqKey="Reungoat E">E Reungoat</name>
</author>
<author><name sortKey="Gentil Dit Maurin, A" uniqKey="Gentil Dit Maurin A">A Gentil dit Maurin</name>
</author>
<author><name sortKey="Varbanov, M" uniqKey="Varbanov M">M Varbanov</name>
</author>
<author><name sortKey="Blaising, J" uniqKey="Blaising J">J Blaising</name>
</author>
<author><name sortKey="Michelet, M" uniqKey="Michelet M">M Michelet</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Le, Q T" uniqKey="Le Q">Q-T Le</name>
</author>
<author><name sortKey="Blanchet, M" uniqKey="Blanchet M">M Blanchet</name>
</author>
<author><name sortKey="Seidah, Ng" uniqKey="Seidah N">NG Seidah</name>
</author>
<author><name sortKey="Labonte, P" uniqKey="Labonte P">P Labonté</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name>
</author>
<author><name sortKey="Vedantham, P" uniqKey="Vedantham P">P Vedantham</name>
</author>
<author><name sortKey="Lu, K" uniqKey="Lu K">K Lu</name>
</author>
<author><name sortKey="Agudelo, J" uniqKey="Agudelo J">J Agudelo</name>
</author>
<author><name sortKey="Carrion, R" uniqKey="Carrion R">R. Carrion</name>
</author>
<author><name sortKey="Nunneley, Jw" uniqKey="Nunneley J">JW Nunneley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cockrell, As" uniqKey="Cockrell A">AS Cockrell</name>
</author>
<author><name sortKey="Peck, Km" uniqKey="Peck K">KM Peck</name>
</author>
<author><name sortKey="Yount, Bl" uniqKey="Yount B">BL Yount</name>
</author>
<author><name sortKey="Agnihothram, Ss" uniqKey="Agnihothram S">SS Agnihothram</name>
</author>
<author><name sortKey="Scobey, T" uniqKey="Scobey T">T Scobey</name>
</author>
<author><name sortKey="Curnes, Nr" uniqKey="Curnes N">NR Curnes</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Barlan, A" uniqKey="Barlan A">A Barlan</name>
</author>
<author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name>
</author>
<author><name sortKey="Sarkar, Mk" uniqKey="Sarkar M">MK Sarkar</name>
</author>
<author><name sortKey="Li, K" uniqKey="Li K">K Li</name>
</author>
<author><name sortKey="Mccray, Pb" uniqKey="Mccray P">PB. McCray</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rosenberger, Cm" uniqKey="Rosenberger C">CM Rosenberger</name>
</author>
<author><name sortKey="Podyminogin, Rl" uniqKey="Podyminogin R">RL Podyminogin</name>
</author>
<author><name sortKey="Askovich, Ps" uniqKey="Askovich P">PS Askovich</name>
</author>
<author><name sortKey="Navarro, G" uniqKey="Navarro G">G Navarro</name>
</author>
<author><name sortKey="Kaiser, Sm" uniqKey="Kaiser S">SM Kaiser</name>
</author>
<author><name sortKey="Sanders, Cj" uniqKey="Sanders C">CJ Sanders</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Whitt, Ma" uniqKey="Whitt M">MA Whitt</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Azhar, Ei" uniqKey="Azhar E">EI Azhar</name>
</author>
<author><name sortKey="El Kafrawy, Sa" uniqKey="El Kafrawy S">SA El-Kafrawy</name>
</author>
<author><name sortKey="Farraj, Sa" uniqKey="Farraj S">SA Farraj</name>
</author>
<author><name sortKey="Hassan, Am" uniqKey="Hassan A">AM Hassan</name>
</author>
<author><name sortKey="Al Saeed, Ms" uniqKey="Al Saeed M">MS Al-Saeed</name>
</author>
<author><name sortKey="Hashem, Am" uniqKey="Hashem A">AM Hashem</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Marcel, Am" uniqKey="Marcel A">AM Marcel</name>
</author>
<author><name sortKey="Victor Max, C" uniqKey="Victor Max C">C Victor Max</name>
</author>
<author><name sortKey="Joerg, J" uniqKey="Joerg J">J Joerg</name>
</author>
<author><name sortKey="Benjamin, M" uniqKey="Benjamin M">M Benjamin</name>
</author>
<author><name sortKey="Mario, Y" uniqKey="Mario Y">Y Mario</name>
</author>
<author><name sortKey="Anne, Ml" uniqKey="Anne M">ML Anne</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cockrell, As" uniqKey="Cockrell A">AS Cockrell</name>
</author>
<author><name sortKey="Yount, Bl" uniqKey="Yount B">BL Yount</name>
</author>
<author><name sortKey="Scobey, T" uniqKey="Scobey T">T Scobey</name>
</author>
<author><name sortKey="Jensen, K" uniqKey="Jensen K">K Jensen</name>
</author>
<author><name sortKey="Douglas, M" uniqKey="Douglas M">M Douglas</name>
</author>
<author><name sortKey="Beall, A" uniqKey="Beall A">A Beall</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Li, K" uniqKey="Li K">K Li</name>
</author>
<author><name sortKey="Wohlford Lenane, Cl" uniqKey="Wohlford Lenane C">CL Wohlford-Lenane</name>
</author>
<author><name sortKey="Channappanavar, R" uniqKey="Channappanavar R">R Channappanavar</name>
</author>
<author><name sortKey="Park, J E" uniqKey="Park J">J-E Park</name>
</author>
<author><name sortKey="Earnest, Jt" uniqKey="Earnest J">JT Earnest</name>
</author>
<author><name sortKey="Bair, Tb" uniqKey="Bair T">TB Bair</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shirato, K" uniqKey="Shirato K">K Shirato</name>
</author>
<author><name sortKey="Kanou, K" uniqKey="Kanou K">K Kanou</name>
</author>
<author><name sortKey="Kawase, M" uniqKey="Kawase M">M Kawase</name>
</author>
<author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S Matsuyama</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Banerjee, I" uniqKey="Banerjee I">I Banerjee</name>
</author>
<author><name sortKey="Yamauchi, Y" uniqKey="Yamauchi Y">Y Yamauchi</name>
</author>
<author><name sortKey="Helenius, A" uniqKey="Helenius A">A Helenius</name>
</author>
<author><name sortKey="Horvath, P" uniqKey="Horvath P">P Horvath</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Simmons, G" uniqKey="Simmons G">G Simmons</name>
</author>
<author><name sortKey="Gosalia, Dn" uniqKey="Gosalia D">DN Gosalia</name>
</author>
<author><name sortKey="Rennekamp, Aj" uniqKey="Rennekamp A">AJ Rennekamp</name>
</author>
<author><name sortKey="Reeves, Jd" uniqKey="Reeves J">JD Reeves</name>
</author>
<author><name sortKey="Diamond, Sl" uniqKey="Diamond S">SL Diamond</name>
</author>
<author><name sortKey="Bates, P" uniqKey="Bates P">P Bates</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Park, J E" uniqKey="Park J">J-E Park</name>
</author>
<author><name sortKey="Li, K" uniqKey="Li K">K Li</name>
</author>
<author><name sortKey="Barlan, A" uniqKey="Barlan A">A Barlan</name>
</author>
<author><name sortKey="Fehr, Ar" uniqKey="Fehr A">AR Fehr</name>
</author>
<author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name>
</author>
<author><name sortKey="Mccray, Pb" uniqKey="Mccray P">PB McCray</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zimmerman, B" uniqKey="Zimmerman B">B Zimmerman</name>
</author>
<author><name sortKey="Kelly, B" uniqKey="Kelly B">B Kelly</name>
</author>
<author><name sortKey="Mcmillan Brian, J" uniqKey="Mcmillan Brian J">J McMillan Brian</name>
</author>
<author><name sortKey="Seegar Tom, Cm" uniqKey="Seegar Tom C">CM Seegar Tom</name>
</author>
<author><name sortKey="Dror Ron, O" uniqKey="Dror Ron O">O Dror Ron</name>
</author>
<author><name sortKey="Kruse Andrew, C" uniqKey="Kruse Andrew C">C Kruse Andrew</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Takano, T" uniqKey="Takano T">T Takano</name>
</author>
<author><name sortKey="Satomi, Y" uniqKey="Satomi Y">Y Satomi</name>
</author>
<author><name sortKey="Oyama, Y" uniqKey="Oyama Y">Y Oyama</name>
</author>
<author><name sortKey="Doki, T" uniqKey="Doki T">T Doki</name>
</author>
<author><name sortKey="Hohdatsu, T" uniqKey="Hohdatsu T">T Hohdatsu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thorp, Eb" uniqKey="Thorp E">EB Thorp</name>
</author>
<author><name sortKey="Gallagher, Tm" uniqKey="Gallagher T">TM Gallagher</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Glende, J" uniqKey="Glende J">J Glende</name>
</author>
<author><name sortKey="Schwegmann Wessels, C" uniqKey="Schwegmann Wessels C">C Schwegmann-Wessels</name>
</author>
<author><name sortKey="Al Falah, M" uniqKey="Al Falah M">M Al-Falah</name>
</author>
<author><name sortKey="Pfefferle, S" uniqKey="Pfefferle S">S Pfefferle</name>
</author>
<author><name sortKey="Qu, X" uniqKey="Qu X">X Qu</name>
</author>
<author><name sortKey="Deng, H" uniqKey="Deng H">H Deng</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Choi, Ks" uniqKey="Choi K">KS Choi</name>
</author>
<author><name sortKey="Aizaki, H" uniqKey="Aizaki H">H Aizaki</name>
</author>
<author><name sortKey="Lai, Mmc" uniqKey="Lai M">MMC Lai</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nomura, R" uniqKey="Nomura R">R Nomura</name>
</author>
<author><name sortKey="Kiyota, A" uniqKey="Kiyota A">A Kiyota</name>
</author>
<author><name sortKey="Suzaki, E" uniqKey="Suzaki E">E Suzaki</name>
</author>
<author><name sortKey="Kataoka, K" uniqKey="Kataoka K">K Kataoka</name>
</author>
<author><name sortKey="Ohe, Y" uniqKey="Ohe Y">Y Ohe</name>
</author>
<author><name sortKey="Miyamoto, K" uniqKey="Miyamoto K">K Miyamoto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Walls, Ac" uniqKey="Walls A">AC Walls</name>
</author>
<author><name sortKey="Tortorici, Ma" uniqKey="Tortorici M">MA Tortorici</name>
</author>
<author><name sortKey="Bosch, B J" uniqKey="Bosch B">B-J Bosch</name>
</author>
<author><name sortKey="Frenz, B" uniqKey="Frenz B">B Frenz</name>
</author>
<author><name sortKey="Rottier, Pjm" uniqKey="Rottier P">PJM Rottier</name>
</author>
<author><name sortKey="Dimaio, F" uniqKey="Dimaio F">F DiMaio</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kirchdoerfer, Rn" uniqKey="Kirchdoerfer R">RN Kirchdoerfer</name>
</author>
<author><name sortKey="Cottrell, Ca" uniqKey="Cottrell C">CA Cottrell</name>
</author>
<author><name sortKey="Wang, N" uniqKey="Wang N">N Wang</name>
</author>
<author><name sortKey="Pallesen, J" uniqKey="Pallesen J">J Pallesen</name>
</author>
<author><name sortKey="Yassine, Hm" uniqKey="Yassine H">HM Yassine</name>
</author>
<author><name sortKey="Turner, Hl" uniqKey="Turner H">HL Turner</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>
<author><name sortKey="Zhang, S" uniqKey="Zhang S">S Zhang</name>
</author>
<author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name>
</author>
<author><name sortKey="Tong, P" uniqKey="Tong P">P Tong</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Klasse, Pj" uniqKey="Klasse P">PJ Klasse</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Millet, Jk" uniqKey="Millet J">JK Millet</name>
</author>
<author><name sortKey="Whittaker, Gr" uniqKey="Whittaker G">GR Whittaker</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gierer, S" uniqKey="Gierer S">S Gierer</name>
</author>
<author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Müller</name>
</author>
<author><name sortKey="Heurich, A" uniqKey="Heurich A">A Heurich</name>
</author>
<author><name sortKey="Ritz, D" uniqKey="Ritz D">D Ritz</name>
</author>
<author><name sortKey="Springstein, Bl" uniqKey="Springstein B">BL Springstein</name>
</author>
<author><name sortKey="Karsten, Cb" uniqKey="Karsten C">CB Karsten</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Belouzard, S" uniqKey="Belouzard S">S Belouzard</name>
</author>
<author><name sortKey="Chu, Vc" uniqKey="Chu V">VC Chu</name>
</author>
<author><name sortKey="Whittaker, Gr" uniqKey="Whittaker G">GR Whittaker</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bosch, Bj" uniqKey="Bosch B">BJ Bosch</name>
</author>
<author><name sortKey="Bartelink, W" uniqKey="Bartelink W">W Bartelink</name>
</author>
<author><name sortKey="Rottier, Pj" uniqKey="Rottier P">PJ Rottier</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Qiu, Z" uniqKey="Qiu Z">Z Qiu</name>
</author>
<author><name sortKey="Hingley, St" uniqKey="Hingley S">ST Hingley</name>
</author>
<author><name sortKey="Simmons, G" uniqKey="Simmons G">G Simmons</name>
</author>
<author><name sortKey="Yu, C" uniqKey="Yu C">C Yu</name>
</author>
<author><name sortKey="Das Sarma, J" uniqKey="Das Sarma J">J Das Sarma</name>
</author>
<author><name sortKey="Bates, P" uniqKey="Bates P">P Bates</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bohley, P" uniqKey="Bohley P">P Bohley</name>
</author>
<author><name sortKey="Seglen, Po" uniqKey="Seglen P">PO Seglen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gierer, S" uniqKey="Gierer S">S Gierer</name>
</author>
<author><name sortKey="Bertram, S" uniqKey="Bertram S">S Bertram</name>
</author>
<author><name sortKey="Kaup, F" uniqKey="Kaup F">F Kaup</name>
</author>
<author><name sortKey="Wrensch, F" uniqKey="Wrensch F">F Wrensch</name>
</author>
<author><name sortKey="Heurich, A" uniqKey="Heurich A">A Heurich</name>
</author>
<author><name sortKey="Kr Mer Kuhl, A" uniqKey="Kr Mer Kuhl A">A Krämer-Kühl</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Meer, G" uniqKey="Van Meer G">G van Meer</name>
</author>
<author><name sortKey="Voelker, Dr" uniqKey="Voelker D">DR Voelker</name>
</author>
<author><name sortKey="Feigenson, Gw" uniqKey="Feigenson G">GW Feigenson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wrensch, F" uniqKey="Wrensch F">F Wrensch</name>
</author>
<author><name sortKey="Winkler, M" uniqKey="Winkler M">M Winkler</name>
</author>
<author><name sortKey="Pohlmann, S" uniqKey="Pohlmann S">S Pohlmann</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Huang, Ic" uniqKey="Huang I">IC Huang</name>
</author>
<author><name sortKey="Bailey, Cc" uniqKey="Bailey C">CC Bailey</name>
</author>
<author><name sortKey="Weyer, Jl" uniqKey="Weyer J">JL Weyer</name>
</author>
<author><name sortKey="Radoshitzky, Sr" uniqKey="Radoshitzky S">SR Radoshitzky</name>
</author>
<author><name sortKey="Becker, Mm" uniqKey="Becker M">MM Becker</name>
</author>
<author><name sortKey="Chiang, Jj" uniqKey="Chiang J">JJ Chiang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yuan, Y" uniqKey="Yuan Y">Y Yuan</name>
</author>
<author><name sortKey="Cao, D" uniqKey="Cao D">D Cao</name>
</author>
<author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name>
</author>
<author><name sortKey="Ma, J" uniqKey="Ma J">J Ma</name>
</author>
<author><name sortKey="Qi, J" uniqKey="Qi J">J Qi</name>
</author>
<author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Loffler, S" uniqKey="Loffler S">S Loffler</name>
</author>
<author><name sortKey="Lottspeich, F" uniqKey="Lottspeich F">F Lottspeich</name>
</author>
<author><name sortKey="Lanza, F" uniqKey="Lanza F">F Lanza</name>
</author>
<author><name sortKey="Azorsa, Do" uniqKey="Azorsa D">DO Azorsa</name>
</author>
<author><name sortKey="Ter Meulen, V" uniqKey="Ter Meulen V">V ter Meulen</name>
</author>
<author><name sortKey="Schneider Schaulies, J" uniqKey="Schneider Schaulies J">J Schneider-Schaulies</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Krementsov, Dn" uniqKey="Krementsov D">DN Krementsov</name>
</author>
<author><name sortKey="Rassam, P" uniqKey="Rassam P">P Rassam</name>
</author>
<author><name sortKey="Margeat, E" uniqKey="Margeat E">E Margeat</name>
</author>
<author><name sortKey="Roy, Nh" uniqKey="Roy N">NH Roy</name>
</author>
<author><name sortKey="Schneider Schaulies, J" uniqKey="Schneider Schaulies J">J Schneider-Schaulies</name>
</author>
<author><name sortKey="Milhiet, P E" uniqKey="Milhiet P">P-E Milhiet</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Weng, J" uniqKey="Weng J">J Weng</name>
</author>
<author><name sortKey="Krementsov, Dn" uniqKey="Krementsov D">DN Krementsov</name>
</author>
<author><name sortKey="Khurana, S" uniqKey="Khurana S">S Khurana</name>
</author>
<author><name sortKey="Roy, Nh" uniqKey="Roy N">NH Roy</name>
</author>
<author><name sortKey="Thali, M" uniqKey="Thali M">M Thali</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Willett, B" uniqKey="Willett B">B Willett</name>
</author>
<author><name sortKey="Hosie, M" uniqKey="Hosie M">M Hosie</name>
</author>
<author><name sortKey="Shaw, A" uniqKey="Shaw A">A Shaw</name>
</author>
<author><name sortKey="Neil, J" uniqKey="Neil J">J Neil</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pique, C" uniqKey="Pique C">C Pique</name>
</author>
<author><name sortKey="Lagaudriere Gesbert, C" uniqKey="Lagaudriere Gesbert C">C Lagaudriere-Gesbert</name>
</author>
<author><name sortKey="Delamarre, L" uniqKey="Delamarre L">L Delamarre</name>
</author>
<author><name sortKey="Rosenberg, Ar" uniqKey="Rosenberg A">AR Rosenberg</name>
</author>
<author><name sortKey="Conjeaud, H" uniqKey="Conjeaud H">H Conjeaud</name>
</author>
<author><name sortKey="Dokhelar, Mc" uniqKey="Dokhelar M">MC Dokhelar</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name>
</author>
<author><name sortKey="Liu, L" uniqKey="Liu L">L Liu</name>
</author>
<author><name sortKey="Che, Y" uniqKey="Che Y">Y Che</name>
</author>
<author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name>
</author>
<author><name sortKey="Jiang, L" uniqKey="Jiang L">L Jiang</name>
</author>
<author><name sortKey="Dong, C" uniqKey="Dong C">C Dong</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bartosch, B" uniqKey="Bartosch B">B Bartosch</name>
</author>
<author><name sortKey="Vitelli, A" uniqKey="Vitelli A">A Vitelli</name>
</author>
<author><name sortKey="Granier, C" uniqKey="Granier C">C Granier</name>
</author>
<author><name sortKey="Goujon, C" uniqKey="Goujon C">C Goujon</name>
</author>
<author><name sortKey="Dubuisson, J" uniqKey="Dubuisson J">J Dubuisson</name>
</author>
<author><name sortKey="Pascale, S" uniqKey="Pascale S">S Pascale</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Scheffer, Kd" uniqKey="Scheffer K">KD Scheffer</name>
</author>
<author><name sortKey="Gawlitza, A" uniqKey="Gawlitza A">A Gawlitza</name>
</author>
<author><name sortKey="Spoden, Ga" uniqKey="Spoden G">GA Spoden</name>
</author>
<author><name sortKey="Zhang, Xa" uniqKey="Zhang X">XA Zhang</name>
</author>
<author><name sortKey="Lambert, C" uniqKey="Lambert C">C Lambert</name>
</author>
<author><name sortKey="Berditchevski, F" uniqKey="Berditchevski F">F Berditchevski</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pileri, P" uniqKey="Pileri P">P Pileri</name>
</author>
<author><name sortKey="Uematsu, Y" uniqKey="Uematsu Y">Y Uematsu</name>
</author>
<author><name sortKey="Campagnoli, S" uniqKey="Campagnoli S">S Campagnoli</name>
</author>
<author><name sortKey="Galli, G" uniqKey="Galli G">G Galli</name>
</author>
<author><name sortKey="Falugi, F" uniqKey="Falugi F">F Falugi</name>
</author>
<author><name sortKey="Petracca, R" uniqKey="Petracca R">R Petracca</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Krieger, Se" uniqKey="Krieger S">SE Krieger</name>
</author>
<author><name sortKey="Zeisel, Mb" uniqKey="Zeisel M">MB Zeisel</name>
</author>
<author><name sortKey="Davis, C" uniqKey="Davis C">C Davis</name>
</author>
<author><name sortKey="Thumann, C" uniqKey="Thumann C">C Thumann</name>
</author>
<author><name sortKey="Harris, Hj" uniqKey="Harris H">HJ Harris</name>
</author>
<author><name sortKey="Schnober, Ek" uniqKey="Schnober E">EK Schnober</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Feneant, L" uniqKey="Feneant L">L Fénéant</name>
</author>
<author><name sortKey="Levy, S" uniqKey="Levy S">S Levy</name>
</author>
<author><name sortKey="Cocquerel, L" uniqKey="Cocquerel L">L Cocquerel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Scheffer, K" uniqKey="Scheffer K">K Scheffer</name>
</author>
<author><name sortKey="Berditchevski, F" uniqKey="Berditchevski F">F Berditchevski</name>
</author>
<author><name sortKey="Florin, L" uniqKey="Florin L">L Florin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shulla, A" uniqKey="Shulla A">A Shulla</name>
</author>
<author><name sortKey="Heald Sargent, T" uniqKey="Heald Sargent T">T Heald-Sargent</name>
</author>
<author><name sortKey="Subramanya, G" uniqKey="Subramanya G">G Subramanya</name>
</author>
<author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name>
</author>
<author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name>
</author>
<author><name sortKey="Gallagher, T" uniqKey="Gallagher T">T Gallagher</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anderson, Rd" uniqKey="Anderson R">RD Anderson</name>
</author>
<author><name sortKey="Haskell, Re" uniqKey="Haskell R">RE Haskell</name>
</author>
<author><name sortKey="Xia, H" uniqKey="Xia H">H Xia</name>
</author>
<author><name sortKey="Roessler, Bj" uniqKey="Roessler B">BJ Roessler</name>
</author>
<author><name sortKey="Davidson, Bl" uniqKey="Davidson B">BL Davidson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Campbell, Em" uniqKey="Campbell E">EM Campbell</name>
</author>
<author><name sortKey="Perez, O" uniqKey="Perez O">O Perez</name>
</author>
<author><name sortKey="Melar, M" uniqKey="Melar M">M Melar</name>
</author>
<author><name sortKey="Hope, Tj" uniqKey="Hope T">TJ Hope</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">PLoS Pathog</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS Pathog</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plospath</journal-id>
<journal-title-group><journal-title>PLoS Pathogens</journal-title>
</journal-title-group>
<issn pub-type="ppub">1553-7366</issn>
<issn pub-type="epub">1553-7374</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, CA USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">28759649</article-id>
<article-id pub-id-type="pmc">5552337</article-id>
<article-id pub-id-type="doi">10.1371/journal.ppat.1006546</article-id>
<article-id pub-id-type="publisher-id">PPATHOGENS-D-17-00715</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Viruses</subject>
<subj-group><subject>RNA viruses</subject>
<subj-group><subject>Coronaviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Medical Microbiology</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Coronaviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Coronaviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Viruses</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Coronaviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Biochemistry</subject>
<subj-group><subject>Enzymology</subject>
<subj-group><subject>Enzymes</subject>
<subj-group><subject>Proteases</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Biochemistry</subject>
<subj-group><subject>Proteins</subject>
<subj-group><subject>Enzymes</subject>
<subj-group><subject>Proteases</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Virology</subject>
<subj-group><subject>Viral Transmission and Infection</subject>
<subj-group><subject>Viral Entry</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Research and analysis methods</subject>
<subj-group><subject>Biological cultures</subject>
<subj-group><subject>Cell lines</subject>
<subj-group><subject>293T cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Cell Biology</subject>
<subj-group><subject>Cellular Structures and Organelles</subject>
<subj-group><subject>Cell Membranes</subject>
<subj-group><subject>Membrane Fusion</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Cell Biology</subject>
<subj-group><subject>Cellular Structures and Organelles</subject>
<subj-group><subject>Cell Membranes</subject>
<subj-group><subject>Membrane Proteins</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Viruses</subject>
<subj-group><subject>DNA viruses</subject>
<subj-group><subject>Adenoviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Medical Microbiology</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Adenoviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Adenoviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Viruses</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Adenoviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Cell Biology</subject>
<subj-group><subject>Cellular Structures and Organelles</subject>
<subj-group><subject>Cell Membranes</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases</article-title>
<alt-title alt-title-type="running-head">CD9 facilitates rapid coronavirus entry</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Earnest</surname>
<given-names>James T.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-4431-4135</contrib-id>
<name><surname>Hantak</surname>
<given-names>Michael P.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Kun</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McCray</surname>
<given-names>Paul B.</given-names>
<suffix>Jr</suffix>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Funding acquisition</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Resources</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-4213-2354</contrib-id>
<name><surname>Perlman</surname>
<given-names>Stanley</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Funding acquisition</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Resources</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8601-5961</contrib-id>
<name><surname>Gallagher</surname>
<given-names>Tom</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Funding acquisition</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Resources</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
</contrib-group>
<aff id="aff001"><label>1</label>
<addr-line>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL, United States of America</addr-line>
</aff>
<aff id="aff002"><label>2</label>
<addr-line>Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America</addr-line>
</aff>
<aff id="aff003"><label>3</label>
<addr-line>Department of Microbiology, University of Iowa, Iowa City, IA, United States of America</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Frieman</surname>
<given-names>Matthew B.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1"><addr-line>University of Maryland School of Medicine, UNITED STATES</addr-line>
</aff>
<author-notes><fn fn-type="COI-statement" id="coi001"><p>The authors have declared that no competing interests exist.</p>
</fn>
<corresp id="cor001">* E-mail: <email>tgallag@luc.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="epub"><day>31</day>
<month>7</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="collection"><month>7</month>
<year>2017</year>
</pub-date>
<volume>13</volume>
<issue>7</issue>
<elocation-id>e1006546</elocation-id>
<history><date date-type="received"><day>31</day>
<month>3</month>
<year>2017</year>
</date>
<date date-type="accepted"><day>21</day>
<month>7</month>
<year>2017</year>
</date>
</history>
<permissions><copyright-statement>© 2017 Earnest et al</copyright-statement>
<copyright-year>2017</copyright-year>
<copyright-holder>Earnest et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="ppat.1006546.pdf"></self-uri>
<abstract><p>Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease. This CD9-facilitated condensation of receptors and proteases allowed MERS-CoV pseudoviruses to enter cells rapidly and efficiently. Without CD9, MERS-CoV viruses were not activated by TTSPs, and they trafficked into endosomes to be cleaved much later and less efficiently by cathepsins. Thus, we identified DPP4:CD9:TTSP as the protein complexes necessary for early, efficient MERS-CoV entry. To evaluate the importance of these complexes in an <italic>in vivo</italic>
CoV infection model, we used recombinant Adenovirus 5 (rAd5) vectors to express human DPP4 in mouse lungs, thereby sensitizing the animals to MERS-CoV infection. When the rAd5-hDPP4 vectors co-expressed small RNAs silencing <italic>Cd9</italic>
or <italic>Tmprss2</italic>
, the animals were significantly less susceptible, indicating that CD9 and TMPRSS2 facilitated robust <italic>in vivo</italic>
MERS-CoV infection of mouse lungs. Furthermore, the S proteins of virulent mouse-adapted MERS-CoVs acquired a CD9-dependent cell entry character, suggesting that CD9 is a selective agent in the evolution of CoV virulence.</p>
</abstract>
<abstract abstract-type="summary"><title>Author summary</title>
<p>Enveloped viruses rank among the most dangerous zoonotically emerging pathogens. Their cell entry often requires multiple transmembrane proteins in the target cell, which may interact with each other to promote viral-cell membrane fusion. Susceptibility to virus infection may correlate with these transmembrane protein interactions. Here we report that the scaffolding tetraspanin protein CD9 links the receptor for MERS-CoV to a membrane fusion-activating protease called TMPRSS2, forming a complex that promotes rapid and efficient infection. The related human CoV strain 229E was also facilitated by CD9, indicating that multiple CoVs depend on tetraspanin-directed clustering of receptors and proteases for efficient cell entry. Reliance on CD9 specifically applied to virulent, <italic>in vivo</italic>
mouse lung-adapted MERS-CoVs, suggesting that the most efficient virus entry pathways in natural respiratory CoV infections are facilitated by tetraspanins. This suggestion was reinforced by selectively regulating gene expression <italic>in vivo</italic>
, using recombinant adenovirus transducing vectors. The findings demonstrated that CD9 facilitated MERS-CoV infections in mice.</p>
</abstract>
<funding-group><award-group id="award001"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000060</institution-id>
<institution>National Institute of Allergy and Infectious Diseases</institution>
</institution-wrap>
</funding-source>
<award-id>P01 AI060699</award-id>
<principal-award-recipient><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-4213-2354</contrib-id>
<name><surname>Perlman</surname>
<given-names>Stanley</given-names>
</name>
</principal-award-recipient>
</award-group>
<funding-statement>This study was supported by a program project grant to SP from the National Institutes of Health, National Institutes of Allergy and Infectious Disease, grant number P01 AI060699. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts><fig-count count="6"></fig-count>
<table-count count="0"></table-count>
<page-count count="22"></page-count>
</counts>
<custom-meta-group><custom-meta><meta-name>PLOS Publication Stage</meta-name>
<meta-value>vor-update-to-uncorrected-proof</meta-value>
</custom-meta>
<custom-meta><meta-name>Publication Update</meta-name>
<meta-value>2017-08-10</meta-value>
</custom-meta>
<custom-meta id="data-availability"><meta-name>Data Availability</meta-name>
<meta-value>All relevant data are within the paper and its Supporting Information files.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes><title>Data Availability</title>
<p>All relevant data are within the paper and its Supporting Information files.</p>
</notes>
</front>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001105 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 001105 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= MersV1 |flux= Pmc |étape= Curation |type= RBID |clé= PMC:5552337 |texte= The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:28759649" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \ | NlmPubMed2Wicri -a MersV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |