MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment
Identifieur interne : 001905 ( Main/Exploration ); précédent : 001904; suivant : 001906MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment
Auteurs : Adriaan H. De Wilde [Pays-Bas] ; V. Stalin Raj [Pays-Bas] ; Diede Oudshoorn [Pays-Bas] ; Theo M. Bestebroer [Pays-Bas] ; Stefan Van Nieuwkoop [Pays-Bas] ; Ronald W. A. L. Limpens [Pays-Bas] ; Clara C. Posthuma [Pays-Bas] ; Yvonne Van Der Meer [Pays-Bas] ; Montserrat Bárcena [Pays-Bas] ; Bart L. Haagmans [Pays-Bas] ; Eric J. Snijder [Pays-Bas] ; Bernadette G. Van Den Hoogen [Pays-Bas]Source :
- The Journal of General Virology [ 0022-1317 ] ; 2013.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (pharmacologie), Ciclosporine (pharmacologie), Coronavirus (), Coronavirus (pathogénicité), Coronavirus (physiologie), Effet cytopathogène viral, Humains, Interféron alpha (pharmacologie), Lignée cellulaire, Membrane cellulaire (ultrastructure), Microscopie électronique à transmission, Réplication virale, Tests de sensibilité microbienne, Évaluation préclinique de médicament.
- MESH :
- pathogénicité : Coronavirus.
- pharmacologie : Antiviraux, Ciclosporine, Interféron alpha.
- physiologie : Coronavirus.
- Animaux, Coronavirus, Effet cytopathogène viral, Humains, Lignée cellulaire, Membrane cellulaire, Microscopie électronique à transmission, Réplication virale, Tests de sensibilité microbienne, Évaluation préclinique de médicament.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (pharmacology), Cell Line, Cell Membrane (ultrastructure), Chlorocebus aethiops, Coronavirus (drug effects), Coronavirus (pathogenicity), Coronavirus (physiology), Cyclosporine (pharmacology), Cytopathogenic Effect, Viral, Drug Evaluation, Preclinical, Humans, Interferon-alpha (pharmacology), Microbial Sensitivity Tests, Microscopy, Electron, Transmission, Virus Replication.
- MESH :
- chemical , pharmacology : Antiviral Agents, Cyclosporine, Interferon-alpha.
- drug effects : Coronavirus.
- pathogenicity : Coronavirus.
- physiology : Coronavirus.
- ultrastructure : Cell Membrane.
- Animals, Cell Line, Chlorocebus aethiops, Cytopathogenic Effect, Viral, Drug Evaluation, Preclinical, Humans, Microbial Sensitivity Tests, Microscopy, Electron, Transmission, Virus Replication.
Abstract
Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. The 2003 outbreak of severe acute respiratory syndrome (SARS) highlighted the potentially lethal consequences of CoV-induced disease in humans. In 2012, a novel CoV (Middle East Respiratory Syndrome coronavirus; MERS-CoV) emerged, causing 49 human cases thus far, of which 23 had a fatal outcome. In this study, we characterized MERS-CoV replication and cytotoxicity in human and monkey cell lines. Electron microscopy of infected Vero cells revealed extensive membrane rearrangements, including the formation of double-membrane vesicles and convoluted membranes, which have been implicated previously in the RNA synthesis of SARS-CoV and other CoVs. Following infection, we observed rapidly increasing viral RNA synthesis and release of high titres of infectious progeny, followed by a pronounced cytopathology. These characteristics were used to develop an assay for antiviral compound screening in 96-well format, which was used to identify cyclosporin A as an inhibitor of MERS-CoV replication in cell culture. Furthermore, MERS-CoV was found to be 50–100 times more sensitive to alpha interferon (IFN-α) treatment than SARS-CoV, an observation that may have important implications for the treatment of MERS-CoV-infected patients. MERS-CoV infection did not prevent the IFN-induced nuclear translocation of phosphorylated STAT1, in contrast to infection with SARS-CoV where this block inhibits the expression of antiviral genes. These findings highlight relevant differences between these distantly related zoonotic CoVs in terms of their interaction with and evasion of the cellular innate immune response.
Url:
DOI: 10.1099/vir.0.052910-0
PubMed: 23620378
PubMed Central: 3749523
Affiliations:
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De Wilde</name><affiliation wicri:level="3"><nlm:aff id="aff1">Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Raj, V Stalin" sort="Raj, V Stalin" uniqKey="Raj V" first="V. Stalin" last="Raj">V. Stalin Raj</name><affiliation wicri:level="3"><nlm:aff id="aff2">Viroscience Lab, Erasmus MC, Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Viroscience Lab, Erasmus MC, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Oudshoorn, Diede" sort="Oudshoorn, Diede" uniqKey="Oudshoorn D" first="Diede" last="Oudshoorn">Diede Oudshoorn</name><affiliation wicri:level="3"><nlm:aff id="aff1">Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name><affiliation wicri:level="3"><nlm:aff id="aff2">Viroscience Lab, Erasmus MC, Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Viroscience Lab, Erasmus MC, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Van Nieuwkoop, Stefan" sort="Van Nieuwkoop, Stefan" uniqKey="Van Nieuwkoop S" first="Stefan" last="Van Nieuwkoop">Stefan Van Nieuwkoop</name><affiliation wicri:level="3"><nlm:aff id="aff2">Viroscience Lab, Erasmus MC, Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Viroscience Lab, Erasmus MC, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Limpens, Ronald W A L" sort="Limpens, Ronald W A L" uniqKey="Limpens R" first="Ronald W. A. L." last="Limpens">Ronald W. A. L. Limpens</name><affiliation wicri:level="3"><nlm:aff id="aff3">Section Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Section Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Posthuma, Clara C" sort="Posthuma, Clara C" uniqKey="Posthuma C" first="Clara C." last="Posthuma">Clara C. Posthuma</name><affiliation wicri:level="3"><nlm:aff id="aff1">Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Van Der Meer, Yvonne" sort="Van Der Meer, Yvonne" uniqKey="Van Der Meer Y" first="Yvonne" last="Van Der Meer">Yvonne Van Der Meer</name><affiliation wicri:level="3"><nlm:aff id="aff1">Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Barcena, Montserrat" sort="Barcena, Montserrat" uniqKey="Barcena M" first="Montserrat" last="Bárcena">Montserrat Bárcena</name><affiliation wicri:level="3"><nlm:aff id="aff3">Section Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Section Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L." last="Haagmans">Bart L. Haagmans</name><affiliation wicri:level="3"><nlm:aff id="aff2">Viroscience Lab, Erasmus MC, Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Viroscience Lab, Erasmus MC, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J." last="Snijder">Eric J. Snijder</name><affiliation wicri:level="3"><nlm:aff id="aff1">Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Van Den Hoogen, Bernadette G" sort="Van Den Hoogen, Bernadette G" uniqKey="Van Den Hoogen B" first="Bernadette G." last="Van Den Hoogen">Bernadette G. Van Den Hoogen</name><affiliation wicri:level="3"><nlm:aff id="aff2">Viroscience Lab, Erasmus MC, Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Viroscience Lab, Erasmus MC, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author></analytic><series><title level="j">The Journal of General Virology</title><idno type="ISSN">0022-1317</idno><idno type="eISSN">1465-2099</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (pharmacology)</term><term>Cell Line</term><term>Cell Membrane (ultrastructure)</term><term>Chlorocebus aethiops</term><term>Coronavirus (drug effects)</term><term>Coronavirus (pathogenicity)</term><term>Coronavirus (physiology)</term><term>Cyclosporine (pharmacology)</term><term>Cytopathogenic Effect, Viral</term><term>Drug Evaluation, Preclinical</term><term>Humans</term><term>Interferon-alpha (pharmacology)</term><term>Microbial Sensitivity Tests</term><term>Microscopy, Electron, Transmission</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antiviraux (pharmacologie)</term><term>Ciclosporine (pharmacologie)</term><term>Coronavirus ()</term><term>Coronavirus (pathogénicité)</term><term>Coronavirus (physiologie)</term><term>Effet cytopathogène viral</term><term>Humains</term><term>Interféron alpha (pharmacologie)</term><term>Lignée cellulaire</term><term>Membrane cellulaire (ultrastructure)</term><term>Microscopie électronique à transmission</term><term>Réplication virale</term><term>Tests de sensibilité microbienne</term><term>Évaluation préclinique de médicament</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Cyclosporine</term><term>Interferon-alpha</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term><term>Ciclosporine</term><term>Interféron alpha</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Cell Membrane</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Cytopathogenic Effect, Viral</term><term>Drug Evaluation, Preclinical</term><term>Humans</term><term>Microbial Sensitivity Tests</term><term>Microscopy, Electron, Transmission</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Coronavirus</term><term>Effet cytopathogène viral</term><term>Humains</term><term>Lignée cellulaire</term><term>Membrane cellulaire</term><term>Microscopie électronique à transmission</term><term>Réplication virale</term><term>Tests de sensibilité microbienne</term><term>Évaluation préclinique de médicament</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. The 2003 outbreak of severe acute respiratory syndrome (SARS) highlighted the potentially lethal consequences of CoV-induced disease in humans. In 2012, a novel CoV (Middle East Respiratory Syndrome coronavirus; MERS-CoV) emerged, causing 49 human cases thus far, of which 23 had a fatal outcome. In this study, we characterized MERS-CoV replication and cytotoxicity in human and monkey cell lines. Electron microscopy of infected Vero cells revealed extensive membrane rearrangements, including the formation of double-membrane vesicles and convoluted membranes, which have been implicated previously in the RNA synthesis of SARS-CoV and other CoVs. Following infection, we observed rapidly increasing viral RNA synthesis and release of high titres of infectious progeny, followed by a pronounced cytopathology. These characteristics were used to develop an assay for antiviral compound screening in 96-well format, which was used to identify cyclosporin A as an inhibitor of MERS-CoV replication in cell culture. Furthermore, MERS-CoV was found to be 50–100 times more sensitive to alpha interferon (IFN-α) treatment than SARS-CoV, an observation that may have important implications for the treatment of MERS-CoV-infected patients. MERS-CoV infection did not prevent the IFN-induced nuclear translocation of phosphorylated STAT1, in contrast to infection with SARS-CoV where this block inhibits the expression of antiviral genes. These findings highlight relevant differences between these distantly related zoonotic CoVs in terms of their interaction with and evasion of the cellular innate immune response.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Belouzard, S" uniqKey="Belouzard S">S. Belouzard</name></author><author><name sortKey="Millet, J K" uniqKey="Millet J">J. K. Millet</name></author><author><name sortKey="Licitra, B N" uniqKey="Licitra B">B. N. Licitra</name></author><author><name sortKey="Whittaker, G R" uniqKey="Whittaker G">G. R. Whittaker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bergman, S J" uniqKey="Bergman S">S. J. Bergman</name></author><author><name sortKey="Ferguson, M C" uniqKey="Ferguson M">M. C. Ferguson</name></author><author><name sortKey="Santanello, C" uniqKey="Santanello C">C. Santanello</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brockway, S M" uniqKey="Brockway S">S. M. Brockway</name></author><author><name sortKey="Clay, C T" uniqKey="Clay C">C. T. Clay</name></author><author><name sortKey="Lu, X T" uniqKey="Lu X">X. T. Lu</name></author><author><name sortKey="Denison, M R" uniqKey="Denison M">M. R. Denison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cameron, M J" uniqKey="Cameron M">M. J. Cameron</name></author><author><name sortKey="Kelvin, A A" uniqKey="Kelvin A">A. A. Kelvin</name></author><author><name sortKey="Leon, A J" uniqKey="Leon A">A. J. Leon</name></author><author><name sortKey="Cameron, C M" uniqKey="Cameron C">C. M. Cameron</name></author><author><name sortKey="Ran, L" uniqKey="Ran L">L. Ran</name></author><author><name sortKey="Xu, L" uniqKey="Xu L">L. Xu</name></author><author><name sortKey="Chu, Y K" uniqKey="Chu Y">Y. K. Chu</name></author><author><name sortKey="Danesh, A" uniqKey="Danesh A">A. Danesh</name></author><author><name sortKey="Fang, Y" uniqKey="Fang Y">Y. Fang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cervantes Barragan, L" uniqKey="Cervantes Barragan L">L. Cervantes-Barragan</name></author><author><name sortKey="Zust, R" uniqKey="Zust R">R. Züst</name></author><author><name sortKey="Weber, F" uniqKey="Weber F">F. Weber</name></author><author><name sortKey="Spiegel, M" uniqKey="Spiegel M">M. Spiegel</name></author><author><name sortKey="Lang, K S" uniqKey="Lang K">K. S. Lang</name></author><author><name sortKey="Akira, S" uniqKey="Akira S">S. Akira</name></author><author><name sortKey="Thiel, V" uniqKey="Thiel V">V. Thiel</name></author><author><name sortKey="Ludewig, B" uniqKey="Ludewig B">B. Ludewig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Groot, R J" uniqKey="De Groot R">R. J. de Groot</name></author><author><name sortKey="Cowley, J A" uniqKey="Cowley J">J. A. Cowley</name></author><author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L. Enjuanes</name></author><author><name sortKey="Faaberg, K S" uniqKey="Faaberg K">K. S. Faaberg</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author><author><name sortKey="Rottier, P J" uniqKey="Rottier P">P. J. Rottier</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author><author><name sortKey="Gorbalenya, A E" uniqKey="Gorbalenya A">A. E. Gorbalenya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Groot, R J" uniqKey="De Groot R">R. J. de Groot</name></author><author><name sortKey="Baker, S C" uniqKey="Baker S">S. C. Baker</name></author><author><name sortKey="Baric, R S" uniqKey="Baric R">R. S. Baric</name></author><author><name sortKey="Brown, C S" uniqKey="Brown C">C. S. Brown</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L. Enjuanes</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R. A. Fouchier</name></author><author><name sortKey="Galiano, M" uniqKey="Galiano M">M. Galiano</name></author><author><name sortKey="Gorbalenya, A E" uniqKey="Gorbalenya A">A. E. Gorbalenya</name></author><author><name sortKey="Other Authors" uniqKey="Other Authors">other authors</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wilde, A H" uniqKey="De Wilde A">A. H. de Wilde</name></author><author><name sortKey="Zevenhoven Dobbe, J C" uniqKey="Zevenhoven Dobbe J">J. C. Zevenhoven-Dobbe</name></author><author><name sortKey="Van Der Meer, Y" uniqKey="Van Der Meer Y">Y. van der Meer</name></author><author><name sortKey="Thiel, V" uniqKey="Thiel V">V. Thiel</name></author><author><name sortKey="Narayanan, K" uniqKey="Narayanan K">K. Narayanan</name></author><author><name sortKey="Makino, S" uniqKey="Makino S">S. Makino</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author><author><name sortKey="Van Hemert, M J" uniqKey="Van Hemert M">M. J. van Hemert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Gunther, S" uniqKey="Gunther S">S. Günther</name></author><author><name sortKey="Preiser, W" uniqKey="Preiser W">W. Preiser</name></author><author><name sortKey="Van Der Werf, S" uniqKey="Van Der Werf S">S. van der Werf</name></author><author><name sortKey="Brodt, H R" uniqKey="Brodt H">H. R. Brodt</name></author><author><name sortKey="Becker, S" uniqKey="Becker S">S. Becker</name></author><author><name sortKey="Rabenau, H" uniqKey="Rabenau H">H. Rabenau</name></author><author><name sortKey="Panning, M" uniqKey="Panning M">M. Panning</name></author><author><name sortKey="Kolesnikova, L" uniqKey="Kolesnikova L">L. Kolesnikova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R. A. Fouchier</name></author><author><name sortKey="Hartwig, N G" uniqKey="Hartwig N">N. G. Hartwig</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T. M. Bestebroer</name></author><author><name sortKey="Niemeyer, B" uniqKey="Niemeyer B">B. Niemeyer</name></author><author><name sortKey="De Jong, J C" uniqKey="De Jong J">J. C. de Jong</name></author><author><name sortKey="Simon, J H" uniqKey="Simon J">J. H. Simon</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A. D. Osterhaus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frieman, M" uniqKey="Frieman M">M. Frieman</name></author><author><name sortKey="Yount, B" uniqKey="Yount B">B. Yount</name></author><author><name sortKey="Heise, M" uniqKey="Heise M">M. Heise</name></author><author><name sortKey="Kopecky Bromberg, S A" uniqKey="Kopecky Bromberg S">S. A. Kopecky-Bromberg</name></author><author><name sortKey="Palese, P" uniqKey="Palese P">P. Palese</name></author><author><name sortKey="Baric, R S" uniqKey="Baric R">R. S. Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garlinghouse, L E" uniqKey="Garlinghouse L">L. E. Garlinghouse</name></author><author><name sortKey="Smith, A L" uniqKey="Smith A">A. L. Smith</name></author><author><name sortKey="Holford, T" uniqKey="Holford T">T. Holford</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gorbalenya, A E" uniqKey="Gorbalenya A">A. E. Gorbalenya</name></author><author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L. Enjuanes</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gosert, R" uniqKey="Gosert R">R. Gosert</name></author><author><name sortKey="Kanjanahaluethai, A" uniqKey="Kanjanahaluethai A">A. Kanjanahaluethai</name></author><author><name sortKey="Egger, D" uniqKey="Egger D">D. Egger</name></author><author><name sortKey="Bienz, K" uniqKey="Bienz K">K. Bienz</name></author><author><name sortKey="Baker, S C" uniqKey="Baker S">S. C. Baker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haagmans, B L" uniqKey="Haagmans B">B. L. Haagmans</name></author><author><name sortKey="Kuiken, T" uniqKey="Kuiken T">T. Kuiken</name></author><author><name sortKey="Martina, B E" uniqKey="Martina B">B. E. Martina</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R. A. Fouchier</name></author><author><name sortKey="Rimmelzwaan, G F" uniqKey="Rimmelzwaan G">G. F. Rimmelzwaan</name></author><author><name sortKey="Van Amerongen, G" uniqKey="Van Amerongen G">G. van Amerongen</name></author><author><name sortKey="Van Riel, D" uniqKey="Van Riel D">D. van Riel</name></author><author><name sortKey="De Jong, T" uniqKey="De Jong T">T. de Jong</name></author><author><name sortKey="Itamura, S" uniqKey="Itamura S">S. Itamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hamre, D" uniqKey="Hamre D">D. Hamre</name></author><author><name sortKey="Procknow, J J" uniqKey="Procknow J">J. J. Procknow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hussain, S" uniqKey="Hussain S">S. Hussain</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author><author><name sortKey="Gallagher, T M" uniqKey="Gallagher T">T. M. Gallagher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huynh, J" uniqKey="Huynh J">J. Huynh</name></author><author><name sortKey="Li, S" uniqKey="Li S">S. Li</name></author><author><name sortKey="Yount, B" uniqKey="Yount B">B. Yount</name></author><author><name sortKey="Smith, A" uniqKey="Smith A">A. Smith</name></author><author><name sortKey="Sturges, L" uniqKey="Sturges L">L. Sturges</name></author><author><name sortKey="Olsen, J C" uniqKey="Olsen J">J. C. Olsen</name></author><author><name sortKey="Nagel, J" uniqKey="Nagel J">J. Nagel</name></author><author><name sortKey="Johnson, J B" uniqKey="Johnson J">J. B. Johnson</name></author><author><name sortKey="Agnihothram, S" uniqKey="Agnihothram S">S. Agnihothram</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kindler, E" uniqKey="Kindler E">E. Kindler</name></author><author><name sortKey="J Nsd Ttir, H R" uniqKey="J Nsd Ttir H">H. R. Jónsdóttir</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D. Muth</name></author><author><name sortKey="Hamming, O J" uniqKey="Hamming O">O. J. Hamming</name></author><author><name sortKey="Hartmann, R" uniqKey="Hartmann R">R. Hartmann</name></author><author><name sortKey="Rodriguez, R" uniqKey="Rodriguez R">R. Rodriguez</name></author><author><name sortKey="Geffers, R" uniqKey="Geffers R">R. Geffers</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R. A. Fouchier</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Knoops, K" uniqKey="Knoops K">K. Knoops</name></author><author><name sortKey="Kikkert, M" uniqKey="Kikkert M">M. Kikkert</name></author><author><name sortKey="Worm, S H" uniqKey="Worm S">S. H. Worm</name></author><author><name sortKey="Zevenhoven Dobbe, J C" uniqKey="Zevenhoven Dobbe J">J. C. Zevenhoven-Dobbe</name></author><author><name sortKey="Van Der Meer, Y" uniqKey="Van Der Meer Y">Y. van der Meer</name></author><author><name sortKey="Koster, A J" uniqKey="Koster A">A. J. Koster</name></author><author><name sortKey="Mommaas, A M" uniqKey="Mommaas A">A. M. Mommaas</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Knoops, K" uniqKey="Knoops K">K. Knoops</name></author><author><name sortKey="Barcena, M" uniqKey="Barcena M">M. Bárcena</name></author><author><name sortKey="Limpens, R W" uniqKey="Limpens R">R. W. Limpens</name></author><author><name sortKey="Koster, A J" uniqKey="Koster A">A. J. Koster</name></author><author><name sortKey="Mommaas, A M" uniqKey="Mommaas A">A. M. Mommaas</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kopecky Bromberg, S A" uniqKey="Kopecky Bromberg S">S. A. Kopecky-Bromberg</name></author><author><name sortKey="Martinez Sobrido, L" uniqKey="Martinez Sobrido L">L. Martinez-Sobrido</name></author><author><name sortKey="Palese, P" uniqKey="Palese P">P. Palese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ksiazek, T G" uniqKey="Ksiazek T">T. G. Ksiazek</name></author><author><name sortKey="Erdman, D" uniqKey="Erdman D">D. Erdman</name></author><author><name sortKey="Goldsmith, C S" uniqKey="Goldsmith C">C. S. Goldsmith</name></author><author><name sortKey="Zaki, S R" uniqKey="Zaki S">S. R. Zaki</name></author><author><name sortKey="Peret, T" uniqKey="Peret T">T. Peret</name></author><author><name sortKey="Emery, S" uniqKey="Emery S">S. Emery</name></author><author><name sortKey="Tong, S" uniqKey="Tong S">S. Tong</name></author><author><name sortKey="Urbani, C" uniqKey="Urbani C">C. Urbani</name></author><author><name sortKey="Comer, J A" uniqKey="Comer J">J. A. Comer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuiken, T" uniqKey="Kuiken T">T. Kuiken</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R. A. Fouchier</name></author><author><name sortKey="Schutten, M" uniqKey="Schutten M">M. Schutten</name></author><author><name sortKey="Rimmelzwaan, G F" uniqKey="Rimmelzwaan G">G. F. Rimmelzwaan</name></author><author><name sortKey="Van Amerongen, G" uniqKey="Van Amerongen G">G. van Amerongen</name></author><author><name sortKey="Van Riel, D" uniqKey="Van Riel D">D. van Riel</name></author><author><name sortKey="Laman, J D" uniqKey="Laman J">J. D. Laman</name></author><author><name sortKey="De Jong, T" uniqKey="De Jong T">T. de Jong</name></author><author><name sortKey="Van Doornum, G" uniqKey="Van Doornum G">G. van Doornum</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, S K" uniqKey="Lau S">S. K. Lau</name></author><author><name sortKey="Woo, P C" uniqKey="Woo P">P. C. Woo</name></author><author><name sortKey="Li, K S" uniqKey="Li K">K. S. Li</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y. Huang</name></author><author><name sortKey="Tsoi, H W" uniqKey="Tsoi H">H. W. Tsoi</name></author><author><name sortKey="Wong, B H" uniqKey="Wong B">B. H. Wong</name></author><author><name sortKey="Wong, S S" uniqKey="Wong S">S. S. Wong</name></author><author><name sortKey="Leung, S Y" uniqKey="Leung S">S. Y. Leung</name></author><author><name sortKey="Chan, K H" uniqKey="Chan K">K. H. Chan</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K. Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Shi, Z" uniqKey="Shi Z">Z. Shi</name></author><author><name sortKey="Yu, M" uniqKey="Yu M">M. Yu</name></author><author><name sortKey="Ren, W" uniqKey="Ren W">W. Ren</name></author><author><name sortKey="Smith, C" uniqKey="Smith C">C. Smith</name></author><author><name sortKey="Epstein, J H" uniqKey="Epstein J">J. H. Epstein</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H. Wang</name></author><author><name sortKey="Crameri, G" uniqKey="Crameri G">G. Crameri</name></author><author><name sortKey="Hu, Z" uniqKey="Hu Z">Z. Hu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcintosh, K" uniqKey="Mcintosh K">K. McIntosh</name></author><author><name sortKey="Dees, J H" uniqKey="Dees J">J. H. Dees</name></author><author><name sortKey="Becker, W B" uniqKey="Becker W">W. B. Becker</name></author><author><name sortKey="Kapikian, A Z" uniqKey="Kapikian A">A. Z. Kapikian</name></author><author><name sortKey="Chanock, R M" uniqKey="Chanock R">R. M. Chanock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muller, M A" uniqKey="Muller M">M. A. Müller</name></author><author><name sortKey="Raj, V S" uniqKey="Raj V">V. S. Raj</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D. Muth</name></author><author><name sortKey="Meyer, B" uniqKey="Meyer B">B. Meyer</name></author><author><name sortKey="Kallies, S" uniqKey="Kallies S">S. Kallies</name></author><author><name sortKey="Smits, S L" uniqKey="Smits S">S. L. Smits</name></author><author><name sortKey="Wollny, R" uniqKey="Wollny R">R. Wollny</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T. M. Bestebroer</name></author><author><name sortKey="Specht, S" uniqKey="Specht S">S. Specht</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagy, P D" uniqKey="Nagy P">P. D. Nagy</name></author><author><name sortKey="Wang, R Y" uniqKey="Wang R">R. Y. Wang</name></author><author><name sortKey="Pogany, J" uniqKey="Pogany J">J. Pogany</name></author><author><name sortKey="Hafren, A" uniqKey="Hafren A">A. Hafren</name></author><author><name sortKey="Makinen, K" uniqKey="Makinen K">K. Makinen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paragas, J" uniqKey="Paragas J">J. Paragas</name></author><author><name sortKey="Blatt, L M" uniqKey="Blatt L">L. M. Blatt</name></author><author><name sortKey="Hartmann, C" uniqKey="Hartmann C">C. Hartmann</name></author><author><name sortKey="Huggins, J W" uniqKey="Huggins J">J. W. Huggins</name></author><author><name sortKey="Endy, T P" uniqKey="Endy T">T. P. Endy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author><author><name sortKey="Netland, J" uniqKey="Netland J">J. Netland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pfefferle, S" uniqKey="Pfefferle S">S. Pfefferle</name></author><author><name sortKey="Oppong, S" uniqKey="Oppong S">S. Oppong</name></author><author><name sortKey="Drexler, J F" uniqKey="Drexler J">J. F. Drexler</name></author><author><name sortKey="Gloza Rausch, F" uniqKey="Gloza Rausch F">F. Gloza-Rausch</name></author><author><name sortKey="Ipsen, A" uniqKey="Ipsen A">A. Ipsen</name></author><author><name sortKey="Seebens, A" uniqKey="Seebens A">A. Seebens</name></author><author><name sortKey="Muller, M A" uniqKey="Muller M">M. A. Müller</name></author><author><name sortKey="Annan, A" uniqKey="Annan A">A. Annan</name></author><author><name sortKey="Vallo, P" uniqKey="Vallo P">P. Vallo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pfefferle, S" uniqKey="Pfefferle S">S. Pfefferle</name></author><author><name sortKey="Schopf, J" uniqKey="Schopf J">J. Schöpf</name></author><author><name sortKey="Kogl, M" uniqKey="Kogl M">M. Kögl</name></author><author><name sortKey="Friedel, C C" uniqKey="Friedel C">C. C. Friedel</name></author><author><name sortKey="Muller, M A" uniqKey="Muller M">M. A. Müller</name></author><author><name sortKey="Carbajo Lozoya, J" uniqKey="Carbajo Lozoya J">J. Carbajo-Lozoya</name></author><author><name sortKey="Stellberger, T" uniqKey="Stellberger T">T. Stellberger</name></author><author><name sortKey="Von Dall Rmi, E" uniqKey="Von Dall Rmi E">E. von Dall’Armi</name></author><author><name sortKey="Herzog, P" uniqKey="Herzog P">P. Herzog</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raj, V S" uniqKey="Raj V">V. S. Raj</name></author><author><name sortKey="Mou, H" uniqKey="Mou H">H. Mou</name></author><author><name sortKey="Smits, S L" uniqKey="Smits S">S. L. Smits</name></author><author><name sortKey="Dekkers, D H" uniqKey="Dekkers D">D. H. Dekkers</name></author><author><name sortKey="Muller, M A" uniqKey="Muller M">M. A. Müller</name></author><author><name sortKey="Dijkman, R" uniqKey="Dijkman R">R. Dijkman</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D. Muth</name></author><author><name sortKey="Demmers, J A" uniqKey="Demmers J">J. A. Demmers</name></author><author><name sortKey="Zaki, A" uniqKey="Zaki A">A. Zaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Randall, R E" uniqKey="Randall R">R. E. Randall</name></author><author><name sortKey="Goodbourn, S" uniqKey="Goodbourn S">S. Goodbourn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ratia, K" uniqKey="Ratia K">K. Ratia</name></author><author><name sortKey="Saikatendu, K S" uniqKey="Saikatendu K">K. S. Saikatendu</name></author><author><name sortKey="Santarsiero, B D" uniqKey="Santarsiero B">B. D. Santarsiero</name></author><author><name sortKey="Barretto, N" uniqKey="Barretto N">N. Barretto</name></author><author><name sortKey="Baker, S C" uniqKey="Baker S">S. C. Baker</name></author><author><name sortKey="Stevens, R C" uniqKey="Stevens R">R. C. Stevens</name></author><author><name sortKey="Mesecar, A D" uniqKey="Mesecar A">A. D. Mesecar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rose, K M" uniqKey="Rose K">K. M. Rose</name></author><author><name sortKey="Elliott, R" uniqKey="Elliott R">R. Elliott</name></author><author><name sortKey="Martinez Sobrido, L" uniqKey="Martinez Sobrido L">L. Martínez-Sobrido</name></author><author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A. García-Sastre</name></author><author><name sortKey="Weiss, S R" uniqKey="Weiss S">S. R. Weiss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roth Cross, J K" uniqKey="Roth Cross J">J. K. Roth-Cross</name></author><author><name sortKey="Martinez Sobrido, L" uniqKey="Martinez Sobrido L">L. Martínez-Sobrido</name></author><author><name sortKey="Scott, E P" uniqKey="Scott E">E. P. Scott</name></author><author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A. García-Sastre</name></author><author><name sortKey="Weiss, S R" uniqKey="Weiss S">S. R. Weiss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sims, A C" uniqKey="Sims A">A. C. Sims</name></author><author><name sortKey="Tilton, S C" uniqKey="Tilton S">S. C. Tilton</name></author><author><name sortKey="Menachery, V D" uniqKey="Menachery V">V. D. Menachery</name></author><author><name sortKey="Gralinski, L E" uniqKey="Gralinski L">L. E. Gralinski</name></author><author><name sortKey="Sch Fer, A" uniqKey="Sch Fer A">A. Schäfer</name></author><author><name sortKey="Matzke, M M" uniqKey="Matzke M">M. M. Matzke</name></author><author><name sortKey="Webb Robertson, B J" uniqKey="Webb Robertson B">B. J. Webb-Robertson</name></author><author><name sortKey="Chang, J" uniqKey="Chang J">J. Chang</name></author><author><name sortKey="Luna, M L" uniqKey="Luna M">M. L. Luna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author><author><name sortKey="Wassenaar, A L" uniqKey="Wassenaar A">A. L. Wassenaar</name></author><author><name sortKey="Spaan, W J" uniqKey="Spaan W">W. J. Spaan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author><author><name sortKey="Bredenbeek, P J" uniqKey="Bredenbeek P">P. J. Bredenbeek</name></author><author><name sortKey="Dobbe, J C" uniqKey="Dobbe J">J. C. Dobbe</name></author><author><name sortKey="Thiel, V" uniqKey="Thiel V">V. Thiel</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author><author><name sortKey="Poon, L L" uniqKey="Poon L">L. L. Poon</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y. Guan</name></author><author><name sortKey="Rozanov, M" uniqKey="Rozanov M">M. Rozanov</name></author><author><name sortKey="Spaan, W J" uniqKey="Spaan W">W. J. Spaan</name></author><author><name sortKey="Gorbalenya, A E" uniqKey="Gorbalenya A">A. E. Gorbalenya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author><author><name sortKey="Van Der Meer, Y" uniqKey="Van Der Meer Y">Y. van der Meer</name></author><author><name sortKey="Zevenhoven Dobbe, J" uniqKey="Zevenhoven Dobbe J">J. Zevenhoven-Dobbe</name></author><author><name sortKey="Onderwater, J J" uniqKey="Onderwater J">J. J. Onderwater</name></author><author><name sortKey="Van Der Meulen, J" uniqKey="Van Der Meulen J">J. van der Meulen</name></author><author><name sortKey="Koerten, H K" uniqKey="Koerten H">H. K. Koerten</name></author><author><name sortKey="Mommaas, A M" uniqKey="Mommaas A">A. M. Mommaas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stertz, S" uniqKey="Stertz S">S. Stertz</name></author><author><name sortKey="Reichelt, M" uniqKey="Reichelt M">M. Reichelt</name></author><author><name sortKey="Spiegel, M" uniqKey="Spiegel M">M. Spiegel</name></author><author><name sortKey="Kuri, T" uniqKey="Kuri T">T. Kuri</name></author><author><name sortKey="Martinez Sobrido, L" uniqKey="Martinez Sobrido L">L. Martínez-Sobrido</name></author><author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A. García-Sastre</name></author><author><name sortKey="Weber, F" uniqKey="Weber F">F. Weber</name></author><author><name sortKey="Kochs, G" uniqKey="Kochs G">G. Kochs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taguchi, F" uniqKey="Taguchi F">F. Taguchi</name></author><author><name sortKey="Siddell, S G" uniqKey="Siddell S">S. G. Siddell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ulasli, M" uniqKey="Ulasli M">M. Ulasli</name></author><author><name sortKey="Verheije, M H" uniqKey="Verheije M">M. H. Verheije</name></author><author><name sortKey="De Haan, C A" uniqKey="De Haan C">C. A. de Haan</name></author><author><name sortKey="Reggiori, F" uniqKey="Reggiori F">F. Reggiori</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><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T. M. Bestebroer</name></author><author><name sortKey="Raj, V S" uniqKey="Raj V">V. S. Raj</name></author><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A. M. Zaki</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A. D. Osterhaus</name></author><author><name sortKey="Haagmans, B L" uniqKey="Haagmans B">B. L. Haagmans</name></author><author><name sortKey="Gorbalenya, A E" uniqKey="Gorbalenya A">A. E. Gorbalenya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Den Worm, S H" uniqKey="Van Den Worm S">S. H. van den Worm</name></author><author><name sortKey="Eriksson, K K" uniqKey="Eriksson K">K. K. Eriksson</name></author><author><name sortKey="Zevenhoven, J C" uniqKey="Zevenhoven J">J. C. Zevenhoven</name></author><author><name sortKey="Weber, F" uniqKey="Weber F">F. Weber</name></author><author><name sortKey="Zust, R" uniqKey="Zust R">R. Züst</name></author><author><name sortKey="Kuri, T" uniqKey="Kuri T">T. Kuri</name></author><author><name sortKey="Dijkman, R" uniqKey="Dijkman R">R. Dijkman</name></author><author><name sortKey="Chang, G" uniqKey="Chang G">G. Chang</name></author><author><name sortKey="Siddell, S G" uniqKey="Siddell S">S. G. Siddell</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, M F" uniqKey="Jebbink M">M. F. Jebbink</name></author><author><name sortKey="Vermeulen Oost, W" uniqKey="Vermeulen Oost W">W. Vermeulen-Oost</name></author><author><name sortKey="Berkhout, R J" uniqKey="Berkhout R">R. J. Berkhout</name></author><author><name sortKey="Wolthers, K C" uniqKey="Wolthers K">K. C. Wolthers</name></author><author><name sortKey="Wertheim Van Dillen, P M" uniqKey="Wertheim Van Dillen P">P. M. Wertheim-van Dillen</name></author><author><name sortKey="Kaandorp, J" uniqKey="Kaandorp J">J. Kaandorp</name></author><author><name sortKey="Spaargaren, J" uniqKey="Spaargaren J">J. Spaargaren</name></author><author><name sortKey="Berkhout, B" uniqKey="Berkhout B">B. Berkhout</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Meer, Y" uniqKey="Van Der Meer Y">Y. van der Meer</name></author><author><name sortKey="Van Tol, H" uniqKey="Van Tol H">H. van Tol</name></author><author><name sortKey="Locker, J K" uniqKey="Locker J">J. K. Locker</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Hemert, M J" uniqKey="Van Hemert M">M. J. van Hemert</name></author><author><name sortKey="De Wilde, A H" uniqKey="De Wilde A">A. H. de Wilde</name></author><author><name sortKey="Gorbalenya, A E" uniqKey="Gorbalenya A">A. E. Gorbalenya</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Hemert, M J" uniqKey="Van Hemert M">M. J. van Hemert</name></author><author><name sortKey="Van Den Worm, S H" uniqKey="Van Den Worm S">S. H. van den Worm</name></author><author><name sortKey="Knoops, K" uniqKey="Knoops K">K. Knoops</name></author><author><name sortKey="Mommaas, A M" uniqKey="Mommaas A">A. M. Mommaas</name></author><author><name sortKey="Gorbalenya, A E" uniqKey="Gorbalenya A">A. E. Gorbalenya</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Kasteren, P B" uniqKey="Van Kasteren P">P. B. van Kasteren</name></author><author><name sortKey="Bailey Elkin, B A" uniqKey="Bailey Elkin B">B. A. Bailey-Elkin</name></author><author><name sortKey="James, T W" uniqKey="James T">T. W. James</name></author><author><name sortKey="Ninaber, D K" uniqKey="Ninaber D">D. K. Ninaber</name></author><author><name sortKey="Beugeling, C" uniqKey="Beugeling C">C. Beugeling</name></author><author><name sortKey="Khajehpour, M" uniqKey="Khajehpour M">M. Khajehpour</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E. J. Snijder</name></author><author><name sortKey="Mark, B L" uniqKey="Mark B">B. L. Mark</name></author><author><name sortKey="Kikkert, M" uniqKey="Kikkert M">M. Kikkert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Versteeg, G A" uniqKey="Versteeg G">G. A. Versteeg</name></author><author><name sortKey="Bredenbeek, P J" uniqKey="Bredenbeek P">P. J. Bredenbeek</name></author><author><name sortKey="Van Den Worm, S H" uniqKey="Van Den Worm S">S. H. van den Worm</name></author><author><name sortKey="Spaan, W J" uniqKey="Spaan W">W. J. Spaan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vijaykrishna, D" uniqKey="Vijaykrishna D">D. Vijaykrishna</name></author><author><name sortKey="Smith, G J" uniqKey="Smith G">G. J. Smith</name></author><author><name sortKey="Zhang, J X" uniqKey="Zhang J">J. X. Zhang</name></author><author><name sortKey="Peiris, J S" uniqKey="Peiris J">J. S. Peiris</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y. Guan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vijgen, L" uniqKey="Vijgen L">L. Vijgen</name></author><author><name sortKey="Keyaerts, E" uniqKey="Keyaerts E">E. Keyaerts</name></author><author><name sortKey="Moes, E" uniqKey="Moes E">E. Moës</name></author><author><name sortKey="Thoelen, I" uniqKey="Thoelen I">I. Thoelen</name></author><author><name sortKey="Wollants, E" uniqKey="Wollants E">E. Wollants</name></author><author><name sortKey="Lemey, P" uniqKey="Lemey P">P. Lemey</name></author><author><name sortKey="Vandamme, A M" uniqKey="Vandamme A">A. M. Vandamme</name></author><author><name sortKey="Van Ranst, M" uniqKey="Van Ranst M">M. Van Ranst</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weber, F" uniqKey="Weber F">F. Weber</name></author><author><name sortKey="Wagner, V" uniqKey="Wagner V">V. Wagner</name></author><author><name sortKey="Rasmussen, S B" uniqKey="Rasmussen S">S. B. Rasmussen</name></author><author><name sortKey="Hartmann, R" uniqKey="Hartmann R">R. Hartmann</name></author><author><name sortKey="Paludan, S R" uniqKey="Paludan S">S. R. Paludan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, P C" uniqKey="Woo P">P. C. Woo</name></author><author><name sortKey="Lau, S K" uniqKey="Lau S">S. K. Lau</name></author><author><name sortKey="Chu, C M" uniqKey="Chu C">C. M. Chu</name></author><author><name sortKey="Chan, K H" uniqKey="Chan K">K. H. Chan</name></author><author><name sortKey="Tsoi, H W" uniqKey="Tsoi H">H. W. Tsoi</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y. Huang</name></author><author><name sortKey="Wong, B H" uniqKey="Wong B">B. H. Wong</name></author><author><name sortKey="Poon, R W" uniqKey="Poon R">R. W. Poon</name></author><author><name sortKey="Cai, J J" uniqKey="Cai J">J. J. Cai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, P C" uniqKey="Woo P">P. C. Woo</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M. Wang</name></author><author><name sortKey="Lau, S K" uniqKey="Lau S">S. K. Lau</name></author><author><name sortKey="Xu, H" uniqKey="Xu H">H. Xu</name></author><author><name sortKey="Poon, R W" uniqKey="Poon R">R. W. Poon</name></author><author><name sortKey="Guo, R" uniqKey="Guo R">R. Guo</name></author><author><name sortKey="Wong, B H" uniqKey="Wong B">B. H. Wong</name></author><author><name sortKey="Gao, K" uniqKey="Gao K">K. Gao</name></author><author><name sortKey="Tsoi, H W" uniqKey="Tsoi H">H. W. Tsoi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshikawa, T" uniqKey="Yoshikawa T">T. Yoshikawa</name></author><author><name sortKey="Hill, T E" uniqKey="Hill T">T. E. Hill</name></author><author><name sortKey="Yoshikawa, N" uniqKey="Yoshikawa N">N. Yoshikawa</name></author><author><name sortKey="Popov, V L" uniqKey="Popov V">V. L. Popov</name></author><author><name sortKey="Galindo, C L" uniqKey="Galindo C">C. L. Galindo</name></author><author><name sortKey="Garner, H R" uniqKey="Garner H">H. R. Garner</name></author><author><name sortKey="Peters, C J" uniqKey="Peters C">C. J. Peters</name></author><author><name sortKey="Tseng, C T" uniqKey="Tseng C">C. T. Tseng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A. M. Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S. van Boheemen</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T. M. Bestebroer</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A. D. Osterhaus</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R. A. Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zeng, F Y" uniqKey="Zeng F">F. Y. Zeng</name></author><author><name sortKey="Chan, C W" uniqKey="Chan C">C. W. Chan</name></author><author><name sortKey="Chan, M N" uniqKey="Chan M">M. N. Chan</name></author><author><name sortKey="Chen, J D" uniqKey="Chen J">J. D. Chen</name></author><author><name sortKey="Chow, K Y" uniqKey="Chow K">K. Y. Chow</name></author><author><name sortKey="Hon, C C" uniqKey="Hon C">C. C. Hon</name></author><author><name sortKey="Hui, K H" uniqKey="Hui K">K. H. Hui</name></author><author><name sortKey="Li, J" uniqKey="Li J">J. Li</name></author><author><name sortKey="Li, V Y" uniqKey="Li V">V. Y. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zheng, B" uniqKey="Zheng B">B. Zheng</name></author><author><name sortKey="He, M L" uniqKey="He M">M. L. He</name></author><author><name sortKey="Wong, K L" uniqKey="Wong K">K. L. Wong</name></author><author><name sortKey="Lum, C T" uniqKey="Lum C">C. T. Lum</name></author><author><name sortKey="Poon, L L" uniqKey="Poon L">L. L. Poon</name></author><author><name sortKey="Peng, Y" uniqKey="Peng Y">Y. Peng</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y. Guan</name></author><author><name sortKey="Lin, M C" uniqKey="Lin M">M. C. Lin</name></author><author><name sortKey="Kung, H F" uniqKey="Kung H">H. F. Kung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhong, Y" uniqKey="Zhong Y">Y. Zhong</name></author><author><name sortKey="Tan, Y W" uniqKey="Tan Y">Y. W. Tan</name></author><author><name sortKey="Liu, D X" uniqKey="Liu D">D. X. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, P" uniqKey="Zhou P">P. Zhou</name></author><author><name sortKey="Li, H" uniqKey="Li H">H. Li</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H. Wang</name></author><author><name sortKey="Wang, L F" uniqKey="Wang L">L. F. Wang</name></author><author><name sortKey="Shi, Z" uniqKey="Shi Z">Z. Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zust, R" uniqKey="Zust R">R. Züst</name></author><author><name sortKey="Cervantes Barragan, L" uniqKey="Cervantes Barragan L">L. Cervantes-Barragan</name></author><author><name sortKey="Habjan, M" uniqKey="Habjan M">M. Habjan</name></author><author><name sortKey="Maier, R" uniqKey="Maier R">R. Maier</name></author><author><name sortKey="Neuman, B W" uniqKey="Neuman B">B. W. Neuman</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author><author><name sortKey="Szretter, K J" uniqKey="Szretter K">K. J. Szretter</name></author><author><name sortKey="Baker, S C" uniqKey="Baker S">S. C. Baker</name></author><author><name sortKey="Barchet, W" uniqKey="Barchet W">W. Barchet</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Pays-Bas</li></country><region><li>Hollande-Méridionale</li></region><settlement><li>Leyde</li><li>Rotterdam</li></settlement></list><tree><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="De Wilde, Adriaan H" sort="De Wilde, Adriaan H" uniqKey="De Wilde A" first="Adriaan H." last="De Wilde">Adriaan H. De Wilde</name></region><name sortKey="Barcena, Montserrat" sort="Barcena, Montserrat" uniqKey="Barcena M" first="Montserrat" last="Bárcena">Montserrat Bárcena</name><name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name><name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L." last="Haagmans">Bart L. Haagmans</name><name sortKey="Limpens, Ronald W A L" sort="Limpens, Ronald W A L" uniqKey="Limpens R" first="Ronald W. A. L." last="Limpens">Ronald W. A. L. Limpens</name><name sortKey="Oudshoorn, Diede" sort="Oudshoorn, Diede" uniqKey="Oudshoorn D" first="Diede" last="Oudshoorn">Diede Oudshoorn</name><name sortKey="Posthuma, Clara C" sort="Posthuma, Clara C" uniqKey="Posthuma C" first="Clara C." last="Posthuma">Clara C. Posthuma</name><name sortKey="Raj, V Stalin" sort="Raj, V Stalin" uniqKey="Raj V" first="V. Stalin" last="Raj">V. Stalin Raj</name><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J." last="Snijder">Eric J. Snijder</name><name sortKey="Van Den Hoogen, Bernadette G" sort="Van Den Hoogen, Bernadette G" uniqKey="Van Den Hoogen B" first="Bernadette G." last="Van Den Hoogen">Bernadette G. Van Den Hoogen</name><name sortKey="Van Der Meer, Yvonne" sort="Van Der Meer, Yvonne" uniqKey="Van Der Meer Y" first="Yvonne" last="Van Der Meer">Yvonne Van Der Meer</name><name sortKey="Van Nieuwkoop, Stefan" sort="Van Nieuwkoop, Stefan" uniqKey="Van Nieuwkoop S" first="Stefan" last="Van Nieuwkoop">Stefan Van Nieuwkoop</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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