Reverse genetic characterization of the natural genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo
Identifieur interne : 000C81 ( Pmc/Checkpoint ); précédent : 000C80; suivant : 000C82Reverse genetic characterization of the natural genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo
Auteurs : Susanne Pfefferle [Allemagne] ; Verena Kr Hling ; Vanessa Ditt [Allemagne] ; Klaus Grywna [Allemagne] ; Elke Mühlberger [Allemagne, États-Unis] ; Christian Drosten [Allemagne]Source :
- Virology Journal [ 1743-422X ] ; 2009.
Abstract
During the outbreak of SARS in 2002/3, a prototype virus was isolated from a patient in Frankfurt/Germany (strain Frankfurt-1). As opposed to all other SARS-Coronavirus strains, Frankfurt-1 has a 45-nucleotide deletion in the transmembrane domain of its ORF 7b protein. When over-expressed in HEK 293 cells, the full-length protein but not the variant with the deletion caused interferon beta induction and cleavage of procaspase 3. To study the role of ORF 7b in the context of virus replication, we cloned a full genome cDNA copy of Frankfurt-1 in a bacterial artificial chromosome downstream of a T7 RNA polymerase promoter. Transfection of capped RNA transcribed from this construct yielded infectious virus that was indistinguishable from the original virus isolate. The presumed Frankfurt-1 ancestor with an intact ORF 7b was reconstructed. In CaCo-2 and HUH7 cells, but not in Vero cells, the variant carrying the ORF 7b deletion had a replicative advantage against the parental virus (4- and 6-fold increase of virus RNA in supernatant, respectively). This effect was neither associated with changes in the induction or secretion of type I interferon, nor with altered induction of apoptosis in cell culture. However, pretreatment of cells with interferon beta caused the deleted virus to replicate to higher titers than the parental strain (3.4-fold in Vero cells, 7.9-fold in CaCo-2 cells).
In Syrian Golden Hamsters inoculated intranasally with 10e4 plaque forming units of either virus, mean titers of infectious virus and viral RNA in the lungs after 24 h were increased 23- and 94.8-fold, respectively, with the deleted virus. This difference could explain earlier observations of enhanced virulence of Frankfurt-1 in Hamsters as compared to other SARS-Coronavirus reference strains and identifies the SARS-CoV 7b protein as an attenuating factor with the SARS-Coronavirus genome. Because attenuation was focused on the early phase of infection
The online version of this article (doi:10.1186/1743-422X-6-131) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/1743-422X-6-131
PubMed: 19698190
PubMed Central: 2739521
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
PMC:2739521Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Reverse genetic characterization of the natural genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein <italic>in-vitro</italic>
and <italic>in-vivo</italic>
</title>
<author><name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.424065.1</institution-id>
<institution-id institution-id-type="ISNI">0000000107013136</institution-id>
<institution>Clinical Virology Group,</institution>
<institution>Bernhard Nocht Institute for Tropical Medicine,</institution>
</institution-wrap>
Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Hamburg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kr Hling, Verena" sort="Kr Hling, Verena" uniqKey="Kr Hling V" first="Verena" last="Kr Hling">Verena Kr Hling</name>
<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.10253.35</institution-id>
<institution-id institution-id-type="ISNI">0000000419369756</institution-id>
<institution>Department of Virology,</institution>
<institution>Philipps University Marburg,</institution>
</institution-wrap>
Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ditt, Vanessa" sort="Ditt, Vanessa" uniqKey="Ditt V" first="Vanessa" last="Ditt">Vanessa Ditt</name>
<affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.15090.3d</institution-id>
<institution-id institution-id-type="ISNI">000000008786803X</institution-id>
<institution>Institute of Virology,</institution>
<institution>University of Bonn Medical Centre,</institution>
</institution-wrap>
Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Bonn</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Grywna, Klaus" sort="Grywna, Klaus" uniqKey="Grywna K" first="Klaus" last="Grywna">Klaus Grywna</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.424065.1</institution-id>
<institution-id institution-id-type="ISNI">0000000107013136</institution-id>
<institution>Clinical Virology Group,</institution>
<institution>Bernhard Nocht Institute for Tropical Medicine,</institution>
</institution-wrap>
Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Hamburg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Muhlberger, Elke" sort="Muhlberger, Elke" uniqKey="Muhlberger E" first="Elke" last="Mühlberger">Elke Mühlberger</name>
<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.10253.35</institution-id>
<institution-id institution-id-type="ISNI">0000000419369756</institution-id>
<institution>Department of Virology,</institution>
<institution>Philipps University Marburg,</institution>
</institution-wrap>
Germany</nlm:aff>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff4">, Boston, USA, National Infectious Diseases Laboratories Institute, Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>, Boston, USA, National Infectious Diseases Laboratories Institute, Hamburg</wicri:regionArea>
<placeName><settlement type="city">Hambourg</settlement>
<region type="land" nuts="2">Hambourg</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.475010.7</institution-id>
<institution-id institution-id-type="ISNI">0000000403675222</institution-id>
<institution>Department of Microbiology,</institution>
<institution>Boston University School of Medicine,</institution>
</institution-wrap>
Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Boston</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.424065.1</institution-id>
<institution-id institution-id-type="ISNI">0000000107013136</institution-id>
<institution>Clinical Virology Group,</institution>
<institution>Bernhard Nocht Institute for Tropical Medicine,</institution>
</institution-wrap>
Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Hamburg</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.15090.3d</institution-id>
<institution-id institution-id-type="ISNI">000000008786803X</institution-id>
<institution>Institute of Virology,</institution>
<institution>University of Bonn Medical Centre,</institution>
</institution-wrap>
Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Bonn</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">19698190</idno>
<idno type="pmc">2739521</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739521</idno>
<idno type="RBID">PMC:2739521</idno>
<idno type="doi">10.1186/1743-422X-6-131</idno>
<date when="2009">2009</date>
<idno type="wicri:Area/Pmc/Corpus">000493</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000493</idno>
<idno type="wicri:Area/Pmc/Curation">000493</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000493</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000C81</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000C81</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Reverse genetic characterization of the natural genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein <italic>in-vitro</italic>
and <italic>in-vivo</italic>
</title>
<author><name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.424065.1</institution-id>
<institution-id institution-id-type="ISNI">0000000107013136</institution-id>
<institution>Clinical Virology Group,</institution>
<institution>Bernhard Nocht Institute for Tropical Medicine,</institution>
</institution-wrap>
Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Hamburg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kr Hling, Verena" sort="Kr Hling, Verena" uniqKey="Kr Hling V" first="Verena" last="Kr Hling">Verena Kr Hling</name>
<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.10253.35</institution-id>
<institution-id institution-id-type="ISNI">0000000419369756</institution-id>
<institution>Department of Virology,</institution>
<institution>Philipps University Marburg,</institution>
</institution-wrap>
Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ditt, Vanessa" sort="Ditt, Vanessa" uniqKey="Ditt V" first="Vanessa" last="Ditt">Vanessa Ditt</name>
<affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.15090.3d</institution-id>
<institution-id institution-id-type="ISNI">000000008786803X</institution-id>
<institution>Institute of Virology,</institution>
<institution>University of Bonn Medical Centre,</institution>
</institution-wrap>
Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Bonn</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Grywna, Klaus" sort="Grywna, Klaus" uniqKey="Grywna K" first="Klaus" last="Grywna">Klaus Grywna</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.424065.1</institution-id>
<institution-id institution-id-type="ISNI">0000000107013136</institution-id>
<institution>Clinical Virology Group,</institution>
<institution>Bernhard Nocht Institute for Tropical Medicine,</institution>
</institution-wrap>
Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Hamburg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Muhlberger, Elke" sort="Muhlberger, Elke" uniqKey="Muhlberger E" first="Elke" last="Mühlberger">Elke Mühlberger</name>
<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.10253.35</institution-id>
<institution-id institution-id-type="ISNI">0000000419369756</institution-id>
<institution>Department of Virology,</institution>
<institution>Philipps University Marburg,</institution>
</institution-wrap>
Germany</nlm:aff>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff4">, Boston, USA, National Infectious Diseases Laboratories Institute, Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>, Boston, USA, National Infectious Diseases Laboratories Institute, Hamburg</wicri:regionArea>
<placeName><settlement type="city">Hambourg</settlement>
<region type="land" nuts="2">Hambourg</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.475010.7</institution-id>
<institution-id institution-id-type="ISNI">0000000403675222</institution-id>
<institution>Department of Microbiology,</institution>
<institution>Boston University School of Medicine,</institution>
</institution-wrap>
Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Boston</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.424065.1</institution-id>
<institution-id institution-id-type="ISNI">0000000107013136</institution-id>
<institution>Clinical Virology Group,</institution>
<institution>Bernhard Nocht Institute for Tropical Medicine,</institution>
</institution-wrap>
Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Hamburg</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.15090.3d</institution-id>
<institution-id institution-id-type="ISNI">000000008786803X</institution-id>
<institution>Institute of Virology,</institution>
<institution>University of Bonn Medical Centre,</institution>
</institution-wrap>
Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Bonn</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Virology Journal</title>
<idno type="eISSN">1743-422X</idno>
<imprint><date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>During the outbreak of SARS in 2002/3, a prototype virus was isolated from a patient in Frankfurt/Germany (strain Frankfurt-1). As opposed to all other SARS-Coronavirus strains, Frankfurt-1 has a 45-nucleotide deletion in the transmembrane domain of its ORF 7b protein. When over-expressed in HEK 293 cells, the full-length protein but not the variant with the deletion caused interferon beta induction and cleavage of procaspase 3. To study the role of ORF 7b in the context of virus replication, we cloned a full genome cDNA copy of Frankfurt-1 in a bacterial artificial chromosome downstream of a T7 RNA polymerase promoter. Transfection of capped RNA transcribed from this construct yielded infectious virus that was indistinguishable from the original virus isolate. The presumed Frankfurt-1 ancestor with an intact ORF 7b was reconstructed. In CaCo-2 and HUH7 cells, but not in Vero cells, the variant carrying the ORF 7b deletion had a replicative advantage against the parental virus (4- and 6-fold increase of virus RNA in supernatant, respectively). This effect was neither associated with changes in the induction or secretion of type I interferon, nor with altered induction of apoptosis in cell culture. However, pretreatment of cells with interferon beta caused the deleted virus to replicate to higher titers than the parental strain (3.4-fold in Vero cells, 7.9-fold in CaCo-2 cells).</p>
<p>In Syrian Golden Hamsters inoculated intranasally with 10e4 plaque forming units of either virus, mean titers of infectious virus and viral RNA in the lungs after 24 h were increased 23- and 94.8-fold, respectively, with the deleted virus. This difference could explain earlier observations of enhanced virulence of Frankfurt-1 in Hamsters as compared to other SARS-Coronavirus reference strains and identifies the SARS-CoV 7b protein as an attenuating factor with the SARS-Coronavirus genome. Because attenuation was focused on the early phase of infection <italic>in-vivo</italic>
, ORF 7b might have contributed to the delayed accumulation of virus in patients that was suggested to have limited the spread of the SARS epidemic.</p>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/1743-422X-6-131) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name>
</author>
<author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name>
</author>
<author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name>
</author>
<author><name sortKey="Stohr, K" uniqKey="Stohr K">K Stohr</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 Gunther</name>
</author>
<author><name sortKey="Preiser, W" uniqKey="Preiser W">W Preiser</name>
</author>
<author><name sortKey="Werf, Svan Der" uniqKey="Werf S">Svan der Werf</name>
</author>
<author><name sortKey="Brodt, Hr" uniqKey="Brodt H">HR 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>
<author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name>
</author>
<author><name sortKey="Berger, A" uniqKey="Berger A">A Berger</name>
</author>
<author><name sortKey="Burguire, Am" uniqKey="Burguire A">AM Burguire</name>
</author>
<author><name sortKey="Cinatl, C" uniqKey="Cinatl C">C Cinatl</name>
</author>
<author><name sortKey="Eickmann, M" uniqKey="Eickmann M">M Eickmann</name>
</author>
<author><name sortKey="Escriou, N" uniqKey="Escriou N">N Escriou</name>
</author>
<author><name sortKey="Grywna, K" uniqKey="Grywna K">K Grywna</name>
</author>
<author><name sortKey="Kramme, S" uniqKey="Kramme S">S Kramme</name>
</author>
<author><name sortKey="Manuguerra, Jc" uniqKey="Manuguerra J">JC Manuguerra</name>
</author>
<author><name sortKey="Muller, S" uniqKey="Muller S">S Muller</name>
</author>
<author><name sortKey="Rickerts, V" uniqKey="Rickerts V">V Rickerts</name>
</author>
<author><name sortKey="Sturmer, M" uniqKey="Sturmer M">M Sturmer</name>
</author>
<author><name sortKey="Vieth, S" uniqKey="Vieth S">S Vieth</name>
</author>
<author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name>
</author>
<author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name>
</author>
<author><name sortKey="Schmitz, H" uniqKey="Schmitz H">H Schmitz</name>
</author>
<author><name sortKey="Doerr, Hw" uniqKey="Doerr H">HW Doerr</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name>
</author>
<author><name sortKey="Preiser, W" uniqKey="Preiser W">W Preiser</name>
</author>
<author><name sortKey="Gunther, S" uniqKey="Gunther S">S Gunther</name>
</author>
<author><name sortKey="Schmitz, H" uniqKey="Schmitz H">H Schmitz</name>
</author>
<author><name sortKey="Doerr, Hw" uniqKey="Doerr H">HW Doerr</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ksiazek, Tg" uniqKey="Ksiazek T">TG Ksiazek</name>
</author>
<author><name sortKey="Erdman, D" uniqKey="Erdman D">D Erdman</name>
</author>
<author><name sortKey="Goldsmith, Cs" uniqKey="Goldsmith C">CS Goldsmith</name>
</author>
<author><name sortKey="Zaki, Sr" uniqKey="Zaki S">SR 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, Ja" uniqKey="Comer J">JA Comer</name>
</author>
<author><name sortKey="Lim, W" uniqKey="Lim W">W Lim</name>
</author>
<author><name sortKey="Rollin, Pe" uniqKey="Rollin P">PE Rollin</name>
</author>
<author><name sortKey="Dowell, Sf" uniqKey="Dowell S">SF Dowell</name>
</author>
<author><name sortKey="Ling, Ae" uniqKey="Ling A">AE Ling</name>
</author>
<author><name sortKey="Humphrey, Cd" uniqKey="Humphrey C">CD Humphrey</name>
</author>
<author><name sortKey="Shieh, Wj" uniqKey="Shieh W">WJ Shieh</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kuiken, T" uniqKey="Kuiken T">T Kuiken</name>
</author>
<author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name>
</author>
<author><name sortKey="Schutten, M" uniqKey="Schutten M">M Schutten</name>
</author>
<author><name sortKey="Rimmelzwaan, Gf" uniqKey="Rimmelzwaan G">GF 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, Jd" uniqKey="Laman J">JD 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>
<author><name sortKey="Lim, W" uniqKey="Lim W">W Lim</name>
</author>
<author><name sortKey="Ling, Ae" uniqKey="Ling A">AE Ling</name>
</author>
<author><name sortKey="Chan, Pk" uniqKey="Chan P">PK Chan</name>
</author>
<author><name sortKey="Tam, Js" uniqKey="Tam J">JS Tam</name>
</author>
<author><name sortKey="Zambon, Mc" uniqKey="Zambon M">MC Zambon</name>
</author>
<author><name sortKey="Gopal, R" uniqKey="Gopal R">R Gopal</name>
</author>
<author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name>
</author>
<author><name sortKey="Werf, Svan Der" uniqKey="Werf S">Svan der Werf</name>
</author>
<author><name sortKey="Escriou, N" uniqKey="Escriou N">N Escriou</name>
</author>
<author><name sortKey="Manuguerra, Jc" uniqKey="Manuguerra J">JC Manuguerra</name>
</author>
<author><name sortKey="Stohr, K" uniqKey="Stohr K">K Stohr</name>
</author>
<author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name>
</author>
<author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rota, Pa" uniqKey="Rota P">PA Rota</name>
</author>
<author><name sortKey="Oberste, Ms" uniqKey="Oberste M">MS Oberste</name>
</author>
<author><name sortKey="Monroe, Ss" uniqKey="Monroe S">SS Monroe</name>
</author>
<author><name sortKey="Nix, Wa" uniqKey="Nix W">WA Nix</name>
</author>
<author><name sortKey="Campagnoli, R" uniqKey="Campagnoli R">R Campagnoli</name>
</author>
<author><name sortKey="Icenogle, Jp" uniqKey="Icenogle J">JP Icenogle</name>
</author>
<author><name sortKey="Penaranda, S" uniqKey="Penaranda S">S Penaranda</name>
</author>
<author><name sortKey="Bankamp, B" uniqKey="Bankamp B">B Bankamp</name>
</author>
<author><name sortKey="Maher, K" uniqKey="Maher K">K Maher</name>
</author>
<author><name sortKey="Chen, Mh" uniqKey="Chen M">MH Chen</name>
</author>
<author><name sortKey="Tong, S" uniqKey="Tong S">S Tong</name>
</author>
<author><name sortKey="Tamin, A" uniqKey="Tamin A">A Tamin</name>
</author>
<author><name sortKey="Lowe, L" uniqKey="Lowe L">L Lowe</name>
</author>
<author><name sortKey="Frace, M" uniqKey="Frace M">M Frace</name>
</author>
<author><name sortKey="Derisi, Jl" uniqKey="Derisi J">JL DeRisi</name>
</author>
<author><name sortKey="Chen, Q" uniqKey="Chen Q">Q Chen</name>
</author>
<author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name>
</author>
<author><name sortKey="Erdman, Dd" uniqKey="Erdman D">DD Erdman</name>
</author>
<author><name sortKey="Peret, Tc" uniqKey="Peret T">TC Peret</name>
</author>
<author><name sortKey="Burns, C" uniqKey="Burns C">C Burns</name>
</author>
<author><name sortKey="Ksiazek, Tg" uniqKey="Ksiazek T">TG Ksiazek</name>
</author>
<author><name sortKey="Rollin, Pe" uniqKey="Rollin P">PE Rollin</name>
</author>
<author><name sortKey="Sanchez, A" uniqKey="Sanchez A">A Sanchez</name>
</author>
<author><name sortKey="Liffick, S" uniqKey="Liffick S">S Liffick</name>
</author>
<author><name sortKey="Holloway, B" uniqKey="Holloway B">B Holloway</name>
</author>
<author><name sortKey="Limor, K" uniqKey="Limor K">K Limor</name>
</author>
<author><name sortKey="Mccaustland, K" uniqKey="Mccaustland K">K McCaustland</name>
</author>
<author><name sortKey="Olsen Rasmussen, M" uniqKey="Olsen Rasmussen M">M Olsen-Rasmussen</name>
</author>
<author><name sortKey="Fouchier, R" uniqKey="Fouchier R">R Fouchier</name>
</author>
<author><name sortKey="Gunther, S" uniqKey="Gunther S">S Gunther</name>
</author>
<author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name>
</author>
<author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name>
</author>
<author><name sortKey="Pallansch, Ma" uniqKey="Pallansch M">MA Pallansch</name>
</author>
<author><name sortKey="Anderson, Lj" uniqKey="Anderson L">LJ Anderson</name>
</author>
<author><name sortKey="Bellini, Wj" uniqKey="Bellini W">WJ Bellini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name>
</author>
<author><name sortKey="Zheng, Bj" uniqKey="Zheng B">BJ Zheng</name>
</author>
<author><name sortKey="He, Yq" uniqKey="He Y">YQ He</name>
</author>
<author><name sortKey="Liu, Xl" uniqKey="Liu X">XL Liu</name>
</author>
<author><name sortKey="Zhuang, Zx" uniqKey="Zhuang Z">ZX Zhuang</name>
</author>
<author><name sortKey="Cheung, Cl" uniqKey="Cheung C">CL Cheung</name>
</author>
<author><name sortKey="Luo, Sw" uniqKey="Luo S">SW Luo</name>
</author>
<author><name sortKey="Li, Ph" uniqKey="Li P">PH Li</name>
</author>
<author><name sortKey="Zhang, Lj" uniqKey="Zhang L">LJ Zhang</name>
</author>
<author><name sortKey="Guan, Yj" uniqKey="Guan Y">YJ Guan</name>
</author>
<author><name sortKey="Butt, Km" uniqKey="Butt K">KM Butt</name>
</author>
<author><name sortKey="Wong, Kl" uniqKey="Wong K">KL Wong</name>
</author>
<author><name sortKey="Chan, Kw" uniqKey="Chan K">KW Chan</name>
</author>
<author><name sortKey="Lim, W" uniqKey="Lim W">W Lim</name>
</author>
<author><name sortKey="Shortridge, Kf" uniqKey="Shortridge K">KF Shortridge</name>
</author>
<author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name>
</author>
<author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name>
</author>
<author><name sortKey="Poon, Ll" uniqKey="Poon L">LL Poon</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name>
</author>
<author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name>
</author>
<author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name>
</author>
<author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name>
</author>
<author><name sortKey="Tsoi, Hw" uniqKey="Tsoi H">HW Tsoi</name>
</author>
<author><name sortKey="Wong, Bh" uniqKey="Wong B">BH Wong</name>
</author>
<author><name sortKey="Wong, Ss" uniqKey="Wong S">SS Wong</name>
</author>
<author><name sortKey="Leung, Sy" uniqKey="Leung S">SY Leung</name>
</author>
<author><name sortKey="Chan, Kh" uniqKey="Chan K">KH Chan</name>
</author>
<author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY 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, Jh" uniqKey="Epstein J">JH 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>
<author><name sortKey="Zhang, H" uniqKey="Zhang H">H Zhang</name>
</author>
<author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name>
</author>
<author><name sortKey="Mceachern, J" uniqKey="Mceachern J">J McEachern</name>
</author>
<author><name sortKey="Field, H" uniqKey="Field H">H Field</name>
</author>
<author><name sortKey="Daszak, P" uniqKey="Daszak P">P Daszak</name>
</author>
<author><name sortKey="Eaton, Bt" uniqKey="Eaton B">BT Eaton</name>
</author>
<author><name sortKey="Zhang, S" uniqKey="Zhang S">S Zhang</name>
</author>
<author><name sortKey="Wang, Lf" uniqKey="Wang L">LF Wang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Poon, Ll" uniqKey="Poon L">LL Poon</name>
</author>
<author><name sortKey="Chu, Dk" uniqKey="Chu D">DK Chu</name>
</author>
<author><name sortKey="Chan, Kh" uniqKey="Chan K">KH Chan</name>
</author>
<author><name sortKey="Wong, Ok" uniqKey="Wong O">OK Wong</name>
</author>
<author><name sortKey="Ellis, Tm" uniqKey="Ellis T">TM Ellis</name>
</author>
<author><name sortKey="Leung, Yh" uniqKey="Leung Y">YH Leung</name>
</author>
<author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name>
</author>
<author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name>
</author>
<author><name sortKey="Suen, Ky" uniqKey="Suen K">KY Suen</name>
</author>
<author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name>
</author>
<author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name>
</author>
<author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tang, Xc" uniqKey="Tang X">XC Tang</name>
</author>
<author><name sortKey="Zhang, Jx" uniqKey="Zhang J">JX Zhang</name>
</author>
<author><name sortKey="Zhang, Sy" uniqKey="Zhang S">SY Zhang</name>
</author>
<author><name sortKey="Wang, P" uniqKey="Wang P">P Wang</name>
</author>
<author><name sortKey="Fan, Xh" uniqKey="Fan X">XH Fan</name>
</author>
<author><name sortKey="Li, Lf" uniqKey="Li L">LF Li</name>
</author>
<author><name sortKey="Li, G" uniqKey="Li G">G Li</name>
</author>
<author><name sortKey="Dong, Bq" uniqKey="Dong B">BQ Dong</name>
</author>
<author><name sortKey="Liu, W" uniqKey="Liu W">W Liu</name>
</author>
<author><name sortKey="Cheung, Cl" uniqKey="Cheung C">CL Cheung</name>
</author>
<author><name sortKey="Xu, Km" uniqKey="Xu K">KM Xu</name>
</author>
<author><name sortKey="Song, Wj" uniqKey="Song W">WJ Song</name>
</author>
<author><name sortKey="Vijaykrishna, D" uniqKey="Vijaykrishna D">D Vijaykrishna</name>
</author>
<author><name sortKey="Poon, Ll" uniqKey="Poon L">LL Poon</name>
</author>
<author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name>
</author>
<author><name sortKey="Smith, Gj" uniqKey="Smith G">GJ Smith</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="Wang, Lf" uniqKey="Wang L">LF Wang</name>
</author>
<author><name sortKey="Shi, Z" uniqKey="Shi Z">Z Shi</name>
</author>
<author><name sortKey="Zhang, S" uniqKey="Zhang S">S Zhang</name>
</author>
<author><name sortKey="Field, H" uniqKey="Field H">H Field</name>
</author>
<author><name sortKey="Daszak, P" uniqKey="Daszak P">P Daszak</name>
</author>
<author><name sortKey="Eaton, Bt" uniqKey="Eaton B">BT Eaton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cavanagh, D" uniqKey="Cavanagh D">D Cavanagh</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Herrewegh, Aa" uniqKey="Herrewegh A">AA Herrewegh</name>
</author>
<author><name sortKey="Smeenk, I" uniqKey="Smeenk I">I Smeenk</name>
</author>
<author><name sortKey="Horzinek, Mc" uniqKey="Horzinek M">MC Horzinek</name>
</author>
<author><name sortKey="Rottier, Pj" uniqKey="Rottier P">PJ Rottier</name>
</author>
<author><name sortKey="De Groot, Rj" uniqKey="De Groot R">RJ de Groot</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Saif, Lj" uniqKey="Saif L">LJ Saif</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 Moes</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, Am" uniqKey="Vandamme A">AM 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="Frieman, Mb" uniqKey="Frieman M">MB Frieman</name>
</author>
<author><name sortKey="Yount, B" uniqKey="Yount B">B Yount</name>
</author>
<author><name sortKey="Sims, Ac" uniqKey="Sims A">AC Sims</name>
</author>
<author><name sortKey="Deming, Dj" uniqKey="Deming D">DJ Deming</name>
</author>
<author><name sortKey="Morrison, Te" uniqKey="Morrison T">TE Morrison</name>
</author>
<author><name sortKey="Sparks, J" uniqKey="Sparks J">J Sparks</name>
</author>
<author><name sortKey="Denison, M" uniqKey="Denison M">M Denison</name>
</author>
<author><name sortKey="Heise, M" uniqKey="Heise M">M Heise</name>
</author>
<author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schaecher, Sr" uniqKey="Schaecher S">SR Schaecher</name>
</author>
<author><name sortKey="Touchette, E" uniqKey="Touchette E">E Touchette</name>
</author>
<author><name sortKey="Schriewer, J" uniqKey="Schriewer J">J Schriewer</name>
</author>
<author><name sortKey="Buller, Rm" uniqKey="Buller R">RM Buller</name>
</author>
<author><name sortKey="Pekosz, A" uniqKey="Pekosz A">A Pekosz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yount, B" uniqKey="Yount B">B Yount</name>
</author>
<author><name sortKey="Roberts, Rs" uniqKey="Roberts R">RS Roberts</name>
</author>
<author><name sortKey="Sims, Ac" uniqKey="Sims A">AC Sims</name>
</author>
<author><name sortKey="Deming, D" uniqKey="Deming D">D Deming</name>
</author>
<author><name sortKey="Frieman, Mb" uniqKey="Frieman M">MB Frieman</name>
</author>
<author><name sortKey="Sparks, J" uniqKey="Sparks J">J Sparks</name>
</author>
<author><name sortKey="Denison, Mr" uniqKey="Denison M">MR Denison</name>
</author>
<author><name sortKey="Davis, N" uniqKey="Davis N">N Davis</name>
</author>
<author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Snijder, Ej" uniqKey="Snijder E">EJ Snijder</name>
</author>
<author><name sortKey="Bredenbeek, Pj" uniqKey="Bredenbeek P">PJ Bredenbeek</name>
</author>
<author><name sortKey="Dobbe, Jc" uniqKey="Dobbe J">JC 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, Ll" uniqKey="Poon L">LL 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, Wj" uniqKey="Spaan W">WJ Spaan</name>
</author>
<author><name sortKey="Gorbalenya, Ae" uniqKey="Gorbalenya A">AE Gorbalenya</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="De Haan, Ca" uniqKey="De Haan C">CA de Haan</name>
</author>
<author><name sortKey="Masters, Ps" uniqKey="Masters P">PS Masters</name>
</author>
<author><name sortKey="Shen, X" uniqKey="Shen X">X Shen</name>
</author>
<author><name sortKey="Weiss, S" uniqKey="Weiss S">S Weiss</name>
</author>
<author><name sortKey="Rottier, Pj" uniqKey="Rottier P">PJ Rottier</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Haijema, Bj" uniqKey="Haijema B">BJ Haijema</name>
</author>
<author><name sortKey="Volders, H" uniqKey="Volders H">H Volders</name>
</author>
<author><name sortKey="Rottier, Pj" uniqKey="Rottier P">PJ Rottier</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Herrewegh, Aa" uniqKey="Herrewegh A">AA Herrewegh</name>
</author>
<author><name sortKey="Vennema, H" uniqKey="Vennema H">H Vennema</name>
</author>
<author><name sortKey="Horzinek, Mc" uniqKey="Horzinek M">MC Horzinek</name>
</author>
<author><name sortKey="Rottier, Pj" uniqKey="Rottier P">PJ Rottier</name>
</author>
<author><name sortKey="De Groot, Rj" uniqKey="De Groot R">RJ de Groot</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ortego, J" uniqKey="Ortego J">J Ortego</name>
</author>
<author><name sortKey="Sola, I" uniqKey="Sola I">I Sola</name>
</author>
<author><name sortKey="Almazan, F" uniqKey="Almazan F">F Almazan</name>
</author>
<author><name sortKey="Ceriani, Je" uniqKey="Ceriani J">JE Ceriani</name>
</author>
<author><name sortKey="Riquelme, C" uniqKey="Riquelme C">C Riquelme</name>
</author>
<author><name sortKey="Balasch, M" uniqKey="Balasch M">M Balasch</name>
</author>
<author><name sortKey="Plana, J" uniqKey="Plana J">J Plana</name>
</author>
<author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L Enjuanes</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chinese, Smec" uniqKey="Chinese S">SMEC Chinese</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chiu, Rw" uniqKey="Chiu R">RW Chiu</name>
</author>
<author><name sortKey="Chim, Ss" uniqKey="Chim S">SS Chim</name>
</author>
<author><name sortKey="Tong, Yk" uniqKey="Tong Y">YK Tong</name>
</author>
<author><name sortKey="Fung, Ks" uniqKey="Fung K">KS Fung</name>
</author>
<author><name sortKey="Chan, Pk" uniqKey="Chan P">PK Chan</name>
</author>
<author><name sortKey="Zhao, Gp" uniqKey="Zhao G">GP Zhao</name>
</author>
<author><name sortKey="Lo, Ym" uniqKey="Lo Y">YM Lo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tang, Jw" uniqKey="Tang J">JW Tang</name>
</author>
<author><name sortKey="Cheung, Jl" uniqKey="Cheung J">JL Cheung</name>
</author>
<author><name sortKey="Chu, Im" uniqKey="Chu I">IM Chu</name>
</author>
<author><name sortKey="Sung, Jj" uniqKey="Sung J">JJ Sung</name>
</author>
<author><name sortKey="Peiris, M" uniqKey="Peiris M">M Peiris</name>
</author>
<author><name sortKey="Chan, Pk" uniqKey="Chan P">PK Chan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rice, Cm" uniqKey="Rice C">CM Rice</name>
</author>
<author><name sortKey="Levis, R" uniqKey="Levis R">R Levis</name>
</author>
<author><name sortKey="Strauss, Jh" uniqKey="Strauss J">JH Strauss</name>
</author>
<author><name sortKey="Huang, Hv" uniqKey="Huang H">HV Huang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Semler, Bl" uniqKey="Semler B">BL Semler</name>
</author>
<author><name sortKey="Dorner, Aj" uniqKey="Dorner A">AJ Dorner</name>
</author>
<author><name sortKey="Wimmer, E" uniqKey="Wimmer E">E Wimmer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Werf, Svan Der" uniqKey="Werf S">Svan der Werf</name>
</author>
<author><name sortKey="Bradley, J" uniqKey="Bradley J">J Bradley</name>
</author>
<author><name sortKey="Wimmer, E" uniqKey="Wimmer E">E Wimmer</name>
</author>
<author><name sortKey="Studier, Fw" uniqKey="Studier F">FW Studier</name>
</author>
<author><name sortKey="Dunn, Jj" uniqKey="Dunn J">JJ Dunn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yount, B" uniqKey="Yount B">B Yount</name>
</author>
<author><name sortKey="Curtis, Km" uniqKey="Curtis K">KM Curtis</name>
</author>
<author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yount, B" uniqKey="Yount B">B Yount</name>
</author>
<author><name sortKey="Curtis, Km" uniqKey="Curtis K">KM Curtis</name>
</author>
<author><name sortKey="Fritz, Ea" uniqKey="Fritz E">EA Fritz</name>
</author>
<author><name sortKey="Hensley, Le" uniqKey="Hensley L">LE Hensley</name>
</author>
<author><name sortKey="Jahrling, Pb" uniqKey="Jahrling P">PB Jahrling</name>
</author>
<author><name sortKey="Prentice, E" uniqKey="Prentice E">E Prentice</name>
</author>
<author><name sortKey="Denison, Mr" uniqKey="Denison M">MR Denison</name>
</author>
<author><name sortKey="Geisbert, Tw" uniqKey="Geisbert T">TW Geisbert</name>
</author>
<author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yount, B" uniqKey="Yount B">B Yount</name>
</author>
<author><name sortKey="Denison, Mr" uniqKey="Denison M">MR Denison</name>
</author>
<author><name sortKey="Weiss, Sr" uniqKey="Weiss S">SR Weiss</name>
</author>
<author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thiel, V" uniqKey="Thiel V">V Thiel</name>
</author>
<author><name sortKey="Herold, J" uniqKey="Herold J">J Herold</name>
</author>
<author><name sortKey="Schelle, B" uniqKey="Schelle B">B Schelle</name>
</author>
<author><name sortKey="Siddell, Sg" uniqKey="Siddell S">SG Siddell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thiel, V" uniqKey="Thiel V">V Thiel</name>
</author>
<author><name sortKey="Siddell, Sg" uniqKey="Siddell S">SG Siddell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Almazan, F" uniqKey="Almazan F">F Almazan</name>
</author>
<author><name sortKey="Dediego, Ml" uniqKey="Dediego M">ML Dediego</name>
</author>
<author><name sortKey="Galan, C" uniqKey="Galan C">C Galan</name>
</author>
<author><name sortKey="Escors, D" uniqKey="Escors D">D Escors</name>
</author>
<author><name sortKey="Alvarez, E" uniqKey="Alvarez E">E Alvarez</name>
</author>
<author><name sortKey="Ortego, J" uniqKey="Ortego J">J Ortego</name>
</author>
<author><name sortKey="Sola, I" uniqKey="Sola I">I Sola</name>
</author>
<author><name sortKey="Zuniga, S" uniqKey="Zuniga S">S Zuniga</name>
</author>
<author><name sortKey="Alonso, S" uniqKey="Alonso S">S Alonso</name>
</author>
<author><name sortKey="Moreno, Jl" uniqKey="Moreno J">JL Moreno</name>
</author>
<author><name sortKey="Nogales, A" uniqKey="Nogales A">A Nogales</name>
</author>
<author><name sortKey="Capiscol, C" uniqKey="Capiscol C">C Capiscol</name>
</author>
<author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L Enjuanes</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Almazan, F" uniqKey="Almazan F">F Almazan</name>
</author>
<author><name sortKey="Gonzalez, Jm" uniqKey="Gonzalez J">JM Gonzalez</name>
</author>
<author><name sortKey="Penzes, Z" uniqKey="Penzes Z">Z Penzes</name>
</author>
<author><name sortKey="Izeta, A" uniqKey="Izeta A">A Izeta</name>
</author>
<author><name sortKey="Calvo, E" uniqKey="Calvo E">E Calvo</name>
</author>
<author><name sortKey="Plana Duran, J" uniqKey="Plana Duran J">J Plana-Duran</name>
</author>
<author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L Enjuanes</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gonzalez, Jm" uniqKey="Gonzalez J">JM Gonzalez</name>
</author>
<author><name sortKey="Penzes, Z" uniqKey="Penzes Z">Z Penzes</name>
</author>
<author><name sortKey="Almazan, F" uniqKey="Almazan F">F Almazan</name>
</author>
<author><name sortKey="Calvo, E" uniqKey="Calvo E">E Calvo</name>
</author>
<author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L Enjuanes</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="St Jean, Jr" uniqKey="St Jean J">JR St-Jean</name>
</author>
<author><name sortKey="Desforges, M" uniqKey="Desforges M">M Desforges</name>
</author>
<author><name sortKey="Almazan, F" uniqKey="Almazan F">F Almazan</name>
</author>
<author><name sortKey="Jacomy, H" uniqKey="Jacomy H">H Jacomy</name>
</author>
<author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L Enjuanes</name>
</author>
<author><name sortKey="Talbot, Pj" uniqKey="Talbot P">PJ Talbot</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schaecher, Sr" uniqKey="Schaecher S">SR Schaecher</name>
</author>
<author><name sortKey="Mackenzie, Jm" uniqKey="Mackenzie J">JM Mackenzie</name>
</author>
<author><name sortKey="Pekosz, A" uniqKey="Pekosz A">A Pekosz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schaecher, Sr" uniqKey="Schaecher S">SR Schaecher</name>
</author>
<author><name sortKey="Diamond, Ms" uniqKey="Diamond M">MS Diamond</name>
</author>
<author><name sortKey="Pekosz, A" uniqKey="Pekosz A">A Pekosz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cinatl, J" uniqKey="Cinatl J">J Cinatl</name>
</author>
<author><name sortKey="Hoever, G" uniqKey="Hoever G">G Hoever</name>
</author>
<author><name sortKey="Morgenstern, B" uniqKey="Morgenstern B">B Morgenstern</name>
</author>
<author><name sortKey="Preiser, W" uniqKey="Preiser W">W Preiser</name>
</author>
<author><name sortKey="Vogel, Ju" uniqKey="Vogel J">JU Vogel</name>
</author>
<author><name sortKey="Hofmann, Wk" uniqKey="Hofmann W">WK Hofmann</name>
</author>
<author><name sortKey="Bauer, G" uniqKey="Bauer G">G Bauer</name>
</author>
<author><name sortKey="Michaelis, M" uniqKey="Michaelis M">M Michaelis</name>
</author>
<author><name sortKey="Rabenau, Hf" uniqKey="Rabenau H">HF Rabenau</name>
</author>
<author><name sortKey="Doerr, Hw" uniqKey="Doerr H">HW Doerr</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cinatl, J" uniqKey="Cinatl J">J Cinatl</name>
</author>
<author><name sortKey="Michaelis, M" uniqKey="Michaelis M">M Michaelis</name>
</author>
<author><name sortKey="Morgenstern, B" uniqKey="Morgenstern B">B Morgenstern</name>
</author>
<author><name sortKey="Doerr, Hw" uniqKey="Doerr H">HW Doerr</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nagata, N" uniqKey="Nagata N">N Nagata</name>
</author>
<author><name sortKey="Iwata, N" uniqKey="Iwata N">N Iwata</name>
</author>
<author><name sortKey="Hasegawa, H" uniqKey="Hasegawa H">H Hasegawa</name>
</author>
<author><name sortKey="Fukushi, S" uniqKey="Fukushi S">S Fukushi</name>
</author>
<author><name sortKey="Harashima, A" uniqKey="Harashima A">A Harashima</name>
</author>
<author><name sortKey="Sato, Y" uniqKey="Sato Y">Y Sato</name>
</author>
<author><name sortKey="Saijo, M" uniqKey="Saijo M">M Saijo</name>
</author>
<author><name sortKey="Taguchi, F" uniqKey="Taguchi F">F Taguchi</name>
</author>
<author><name sortKey="Morikawa, S" uniqKey="Morikawa S">S Morikawa</name>
</author>
<author><name sortKey="Sata, T" uniqKey="Sata T">T Sata</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nagata, N" uniqKey="Nagata N">N Nagata</name>
</author>
<author><name sortKey="Iwata, N" uniqKey="Iwata N">N Iwata</name>
</author>
<author><name sortKey="Hasegawa, H" uniqKey="Hasegawa H">H Hasegawa</name>
</author>
<author><name sortKey="Fukushi, S" uniqKey="Fukushi S">S Fukushi</name>
</author>
<author><name sortKey="Yokoyama, M" uniqKey="Yokoyama M">M Yokoyama</name>
</author>
<author><name sortKey="Harashima, A" uniqKey="Harashima A">A Harashima</name>
</author>
<author><name sortKey="Sato, Y" uniqKey="Sato Y">Y Sato</name>
</author>
<author><name sortKey="Saijo, M" uniqKey="Saijo M">M Saijo</name>
</author>
<author><name sortKey="Morikawa, S" uniqKey="Morikawa S">S Morikawa</name>
</author>
<author><name sortKey="Sata, T" uniqKey="Sata T">T Sata</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tan, Yj" uniqKey="Tan Y">YJ Tan</name>
</author>
<author><name sortKey="Fielding, Bc" uniqKey="Fielding B">BC Fielding</name>
</author>
<author><name sortKey="Goh, Py" uniqKey="Goh P">PY Goh</name>
</author>
<author><name sortKey="Shen, S" uniqKey="Shen S">S Shen</name>
</author>
<author><name sortKey="Tan, Th" uniqKey="Tan T">TH Tan</name>
</author>
<author><name sortKey="Lim, Sg" uniqKey="Lim S">SG Lim</name>
</author>
<author><name sortKey="Hong, W" uniqKey="Hong W">W Hong</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tan, Yx" uniqKey="Tan Y">YX Tan</name>
</author>
<author><name sortKey="Tan, Th" uniqKey="Tan T">TH Tan</name>
</author>
<author><name sortKey="Lee, Mj" uniqKey="Lee M">MJ Lee</name>
</author>
<author><name sortKey="Tham, Py" uniqKey="Tham P">PY Tham</name>
</author>
<author><name sortKey="Gunalan, V" uniqKey="Gunalan V">V Gunalan</name>
</author>
<author><name sortKey="Druce, J" uniqKey="Druce J">J Druce</name>
</author>
<author><name sortKey="Birch, C" uniqKey="Birch C">C Birch</name>
</author>
<author><name sortKey="Catton, M" uniqKey="Catton M">M Catton</name>
</author>
<author><name sortKey="Fu, Ny" uniqKey="Fu N">NY Fu</name>
</author>
<author><name sortKey="Yu, Vc" uniqKey="Yu V">VC Yu</name>
</author>
<author><name sortKey="Tan, Yj" uniqKey="Tan Y">YJ Tan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Basler, Cf" uniqKey="Basler C">CF Basler</name>
</author>
<author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name>
</author>
<author><name sortKey="Muhlberger, E" uniqKey="Muhlberger E">E Muhlberger</name>
</author>
<author><name sortKey="Volchkov, V" uniqKey="Volchkov V">V Volchkov</name>
</author>
<author><name sortKey="Paragas, J" uniqKey="Paragas J">J Paragas</name>
</author>
<author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name>
</author>
<author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A Garcia-Sastre</name>
</author>
<author><name sortKey="Palese, P" uniqKey="Palese P">P Palese</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cardenas, Wb" uniqKey="Cardenas W">WB Cardenas</name>
</author>
<author><name sortKey="Loo, Ym" uniqKey="Loo Y">YM Loo</name>
</author>
<author><name sortKey="Gale, M" uniqKey="Gale M">M Gale</name>
</author>
<author><name sortKey="Hartman, Al" uniqKey="Hartman A">AL Hartman</name>
</author>
<author><name sortKey="Kimberlin, Cr" uniqKey="Kimberlin C">CR Kimberlin</name>
</author>
<author><name sortKey="Martinez Sobrido, L" uniqKey="Martinez Sobrido L">L Martinez-Sobrido</name>
</author>
<author><name sortKey="Saphire, Eo" uniqKey="Saphire E">EO Saphire</name>
</author>
<author><name sortKey="Basler, Cf" uniqKey="Basler C">CF Basler</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Spiegel, M" uniqKey="Spiegel M">M Spiegel</name>
</author>
<author><name sortKey="Weber, F" uniqKey="Weber F">F Weber</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kaufmann, Sh" uniqKey="Kaufmann S">SH Kaufmann</name>
</author>
<author><name sortKey="Desnoyers, S" uniqKey="Desnoyers S">S Desnoyers</name>
</author>
<author><name sortKey="Ottaviano, Y" uniqKey="Ottaviano Y">Y Ottaviano</name>
</author>
<author><name sortKey="Davidson, Ne" uniqKey="Davidson N">NE Davidson</name>
</author>
<author><name sortKey="Poirier, Gg" uniqKey="Poirier G">GG Poirier</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roberts, A" uniqKey="Roberts A">A Roberts</name>
</author>
<author><name sortKey="Lamirande, Ew" uniqKey="Lamirande E">EW Lamirande</name>
</author>
<author><name sortKey="Vogel, L" uniqKey="Vogel L">L Vogel</name>
</author>
<author><name sortKey="Jackson, Jp" uniqKey="Jackson J">JP Jackson</name>
</author>
<author><name sortKey="Paddock, Cd" uniqKey="Paddock C">CD Paddock</name>
</author>
<author><name sortKey="Guarner, J" uniqKey="Guarner J">J Guarner</name>
</author>
<author><name sortKey="Zaki, Sr" uniqKey="Zaki S">SR Zaki</name>
</author>
<author><name sortKey="Sheahan, T" uniqKey="Sheahan T">T Sheahan</name>
</author>
<author><name sortKey="Baric, R" uniqKey="Baric R">R Baric</name>
</author>
<author><name sortKey="Subbarao, K" uniqKey="Subbarao K">K Subbarao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roberts, A" uniqKey="Roberts A">A Roberts</name>
</author>
<author><name sortKey="Vogel, L" uniqKey="Vogel L">L Vogel</name>
</author>
<author><name sortKey="Guarner, J" uniqKey="Guarner J">J Guarner</name>
</author>
<author><name sortKey="Hayes, N" uniqKey="Hayes N">N Hayes</name>
</author>
<author><name sortKey="Murphy, B" uniqKey="Murphy B">B Murphy</name>
</author>
<author><name sortKey="Zaki, S" uniqKey="Zaki S">S Zaki</name>
</author>
<author><name sortKey="Subbarao, K" uniqKey="Subbarao K">K Subbarao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Racaniello, Vr" uniqKey="Racaniello V">VR Racaniello</name>
</author>
<author><name sortKey="Baltimore, D" uniqKey="Baltimore D">D Baltimore</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Almazan, F" uniqKey="Almazan F">F Almazan</name>
</author>
<author><name sortKey="Galan, C" uniqKey="Galan C">C Galan</name>
</author>
<author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L Enjuanes</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L Enjuanes</name>
</author>
<author><name sortKey="Sola, I" uniqKey="Sola I">I Sola</name>
</author>
<author><name sortKey="Alonso, S" uniqKey="Alonso S">S Alonso</name>
</author>
<author><name sortKey="Escors, D" uniqKey="Escors D">D Escors</name>
</author>
<author><name sortKey="Zuniga, S" uniqKey="Zuniga S">S Zuniga</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ortego, J" uniqKey="Ortego J">J Ortego</name>
</author>
<author><name sortKey="Escors, D" uniqKey="Escors D">D Escors</name>
</author>
<author><name sortKey="Laude, H" uniqKey="Laude H">H Laude</name>
</author>
<author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L Enjuanes</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Devaraj, Sg" uniqKey="Devaraj S">SG Devaraj</name>
</author>
<author><name sortKey="Wang, N" uniqKey="Wang N">N Wang</name>
</author>
<author><name sortKey="Chen, Z" uniqKey="Chen Z">Z Chen</name>
</author>
<author><name sortKey="Chen, Z" uniqKey="Chen Z">Z Chen</name>
</author>
<author><name sortKey="Tseng, M" uniqKey="Tseng M">M Tseng</name>
</author>
<author><name sortKey="Barretto, N" uniqKey="Barretto N">N Barretto</name>
</author>
<author><name sortKey="Lin, R" uniqKey="Lin R">R Lin</name>
</author>
<author><name sortKey="Peters, Cj" uniqKey="Peters C">CJ Peters</name>
</author>
<author><name sortKey="Tseng, Ct" uniqKey="Tseng C">CT Tseng</name>
</author>
<author><name sortKey="Baker, Sc" uniqKey="Baker S">SC Baker</name>
</author>
<author><name sortKey="Li, K" uniqKey="Li K">K Li</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zust, R" uniqKey="Zust R">R Zust</name>
</author>
<author><name sortKey="Cervantes Barragan, L" uniqKey="Cervantes Barragan L">L Cervantes-Barragan</name>
</author>
<author><name sortKey="Kuri, T" uniqKey="Kuri T">T Kuri</name>
</author>
<author><name sortKey="Blakqori, G" uniqKey="Blakqori G">G Blakqori</name>
</author>
<author><name sortKey="Weber, F" uniqKey="Weber F">F Weber</name>
</author>
<author><name sortKey="Ludewig, B" uniqKey="Ludewig B">B Ludewig</name>
</author>
<author><name sortKey="Thiel, V" uniqKey="Thiel V">V Thiel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Versteeg, Ga" uniqKey="Versteeg G">GA Versteeg</name>
</author>
<author><name sortKey="Bredenbeek, Pj" uniqKey="Bredenbeek P">PJ Bredenbeek</name>
</author>
<author><name sortKey="Worm, Shvan Den" uniqKey="Worm S">SHvan den Worm</name>
</author>
<author><name sortKey="Spaan, Wj" uniqKey="Spaan W">WJ Spaan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kopecky Bromberg, Sa" uniqKey="Kopecky Bromberg S">SA Kopecky-Bromberg</name>
</author>
<author><name sortKey="Martinez Sobrido, L" uniqKey="Martinez Sobrido L">L Martinez-Sobrido</name>
</author>
<author><name sortKey="Frieman, M" uniqKey="Frieman M">M Frieman</name>
</author>
<author><name sortKey="Baric, Ra" uniqKey="Baric R">RA Baric</name>
</author>
<author><name sortKey="Palese, P" uniqKey="Palese P">P Palese</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Frieman, M" uniqKey="Frieman M">M Frieman</name>
</author>
<author><name sortKey="Heise, M" uniqKey="Heise M">M Heise</name>
</author>
<author><name sortKey="Baric, R" uniqKey="Baric R">R Baric</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Hemert, Mj" uniqKey="Van Hemert M">MJ van Hemert</name>
</author>
<author><name sortKey="Worm, Shvan Den" uniqKey="Worm S">SHvan den Worm</name>
</author>
<author><name sortKey="Knoops, K" uniqKey="Knoops K">K Knoops</name>
</author>
<author><name sortKey="Mommaas, Am" uniqKey="Mommaas A">AM Mommaas</name>
</author>
<author><name sortKey="Gorbalenya, Ae" uniqKey="Gorbalenya A">AE Gorbalenya</name>
</author>
<author><name sortKey="Snijder, Ej" uniqKey="Snijder E">EJ Snijder</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, Sa" uniqKey="Kopecky Bromberg S">SA Kopecky-Bromberg</name>
</author>
<author><name sortKey="Palese, P" uniqKey="Palese P">P Palese</name>
</author>
<author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ye, Y" uniqKey="Ye Y">Y Ye</name>
</author>
<author><name sortKey="Hauns, K" uniqKey="Hauns K">K Hauns</name>
</author>
<author><name sortKey="Langland, Jo" uniqKey="Langland J">JO Langland</name>
</author>
<author><name sortKey="Jacobs, Bl" uniqKey="Jacobs B">BL Jacobs</name>
</author>
<author><name sortKey="Hogue, Bg" uniqKey="Hogue B">BG Hogue</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Spiegel, M" uniqKey="Spiegel M">M Spiegel</name>
</author>
<author><name sortKey="Pichlmair, A" uniqKey="Pichlmair A">A Pichlmair</name>
</author>
<author><name sortKey="Muhlberger, E" uniqKey="Muhlberger E">E Muhlberger</name>
</author>
<author><name sortKey="Haller, O" uniqKey="Haller O">O Haller</name>
</author>
<author><name sortKey="Weber, F" uniqKey="Weber F">F Weber</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fraser, C" uniqKey="Fraser C">C Fraser</name>
</author>
<author><name sortKey="Riley, S" uniqKey="Riley S">S Riley</name>
</author>
<author><name sortKey="Anderson, Rm" uniqKey="Anderson R">RM Anderson</name>
</author>
<author><name sortKey="Ferguson, Nm" uniqKey="Ferguson N">NM Ferguson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anderson, Rm" uniqKey="Anderson R">RM Anderson</name>
</author>
<author><name sortKey="Fraser, C" uniqKey="Fraser C">C Fraser</name>
</author>
<author><name sortKey="Ghani, Ac" uniqKey="Ghani A">AC Ghani</name>
</author>
<author><name sortKey="Donnelly, Ca" uniqKey="Donnelly C">CA Donnelly</name>
</author>
<author><name sortKey="Riley, S" uniqKey="Riley S">S Riley</name>
</author>
<author><name sortKey="Ferguson, Nm" uniqKey="Ferguson N">NM Ferguson</name>
</author>
<author><name sortKey="Leung, Gm" uniqKey="Leung G">GM Leung</name>
</author>
<author><name sortKey="Lam, Th" uniqKey="Lam T">TH Lam</name>
</author>
<author><name sortKey="Hedley, Aj" uniqKey="Hedley A">AJ Hedley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name>
</author>
<author><name sortKey="Chu, Cm" uniqKey="Chu C">CM Chu</name>
</author>
<author><name sortKey="Cheng, Vc" uniqKey="Cheng V">VC Cheng</name>
</author>
<author><name sortKey="Chan, Ks" uniqKey="Chan K">KS Chan</name>
</author>
<author><name sortKey="Hung, If" uniqKey="Hung I">IF Hung</name>
</author>
<author><name sortKey="Poon, Ll" uniqKey="Poon L">LL Poon</name>
</author>
<author><name sortKey="Law, Ki" uniqKey="Law K">KI Law</name>
</author>
<author><name sortKey="Tang, Bs" uniqKey="Tang B">BS Tang</name>
</author>
<author><name sortKey="Hon, Ty" uniqKey="Hon T">TY Hon</name>
</author>
<author><name sortKey="Chan, Cs" uniqKey="Chan C">CS Chan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thiel, V" uniqKey="Thiel V">V Thiel</name>
</author>
<author><name sortKey="Ivanov, Ka" uniqKey="Ivanov K">KA Ivanov</name>
</author>
<author><name sortKey="Putics, A" uniqKey="Putics A">A Putics</name>
</author>
<author><name sortKey="Hertzig, T" uniqKey="Hertzig T">T Hertzig</name>
</author>
<author><name sortKey="Schelle, B" uniqKey="Schelle B">B Schelle</name>
</author>
<author><name sortKey="Bayer, S" uniqKey="Bayer S">S Bayer</name>
</author>
<author><name sortKey="Weissbrich, B" uniqKey="Weissbrich B">B Weissbrich</name>
</author>
<author><name sortKey="Snijder, Ej" uniqKey="Snijder E">EJ Snijder</name>
</author>
<author><name sortKey="Rabenau, H" uniqKey="Rabenau H">H Rabenau</name>
</author>
<author><name sortKey="Doerr, Hw" uniqKey="Doerr H">HW Doerr</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Matrosovich, M" uniqKey="Matrosovich M">M Matrosovich</name>
</author>
<author><name sortKey="Matrosovich, T" uniqKey="Matrosovich T">T Matrosovich</name>
</author>
<author><name sortKey="Garten, W" uniqKey="Garten W">W Garten</name>
</author>
<author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name>
</author>
<author><name sortKey="Gui, C" uniqKey="Gui C">C Gui</name>
</author>
<author><name sortKey="Luo, X" uniqKey="Luo X">X Luo</name>
</author>
<author><name sortKey="Yang, Q" uniqKey="Yang Q">Q Yang</name>
</author>
<author><name sortKey="Gunther, S" uniqKey="Gunther S">S Gunther</name>
</author>
<author><name sortKey="Scandella, E" uniqKey="Scandella E">E Scandella</name>
</author>
<author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name>
</author>
<author><name sortKey="Bai, D" uniqKey="Bai D">D Bai</name>
</author>
<author><name sortKey="He, X" uniqKey="He X">X He</name>
</author>
<author><name sortKey="Ludewig, B" uniqKey="Ludewig B">B Ludewig</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Niwa, H" uniqKey="Niwa H">H Niwa</name>
</author>
<author><name sortKey="Yamamura, K" uniqKey="Yamamura K">K Yamamura</name>
</author>
<author><name sortKey="Miyazaki, J" uniqKey="Miyazaki J">J Miyazaki</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">Virol J</journal-id>
<journal-id journal-id-type="iso-abbrev">Virol. J</journal-id>
<journal-title-group><journal-title>Virology Journal</journal-title>
</journal-title-group>
<issn pub-type="epub">1743-422X</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">19698190</article-id>
<article-id pub-id-type="pmc">2739521</article-id>
<article-id pub-id-type="publisher-id">645</article-id>
<article-id pub-id-type="doi">10.1186/1743-422X-6-131</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Reverse genetic characterization of the natural genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein <italic>in-vitro</italic>
and <italic>in-vivo</italic>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Pfefferle</surname>
<given-names>Susanne</given-names>
</name>
<address><email>pfefferle@bni-hamburg.de</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Krähling</surname>
<given-names>Verena</given-names>
</name>
<address><email>kraehliv@staff.uni-marburg.de</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ditt</surname>
<given-names>Vanessa</given-names>
</name>
<address><email>ditt@virology-bonn.de</email>
</address>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Grywna</surname>
<given-names>Klaus</given-names>
</name>
<address><email>grywna@virology-bonn.de</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mühlberger</surname>
<given-names>Elke</given-names>
</name>
<address><email>muehlber@bu.edu</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff4">4</xref>
<xref ref-type="aff" rid="Aff5">5</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Drosten</surname>
<given-names>Christian</given-names>
</name>
<address><email>drosten@virology-bonn.de</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<aff id="Aff1"><label>1</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.424065.1</institution-id>
<institution-id institution-id-type="ISNI">0000000107013136</institution-id>
<institution>Clinical Virology Group,</institution>
<institution>Bernhard Nocht Institute for Tropical Medicine,</institution>
</institution-wrap>
Hamburg, Germany</aff>
<aff id="Aff2"><label>2</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.10253.35</institution-id>
<institution-id institution-id-type="ISNI">0000000419369756</institution-id>
<institution>Department of Virology,</institution>
<institution>Philipps University Marburg,</institution>
</institution-wrap>
Germany</aff>
<aff id="Aff3"><label>3</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.15090.3d</institution-id>
<institution-id institution-id-type="ISNI">000000008786803X</institution-id>
<institution>Institute of Virology,</institution>
<institution>University of Bonn Medical Centre,</institution>
</institution-wrap>
Bonn, Germany</aff>
<aff id="Aff4"><label>4</label>
, Boston, USA, National Infectious Diseases Laboratories Institute, Hamburg, Germany</aff>
<aff id="Aff5"><label>5</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.475010.7</institution-id>
<institution-id institution-id-type="ISNI">0000000403675222</institution-id>
<institution>Department of Microbiology,</institution>
<institution>Boston University School of Medicine,</institution>
</institution-wrap>
Boston, USA</aff>
</contrib-group>
<pub-date pub-type="epub"><day>24</day>
<month>8</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>24</day>
<month>8</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="collection"><year>2009</year>
</pub-date>
<volume>6</volume>
<elocation-id>131</elocation-id>
<history><date date-type="received"><day>30</day>
<month>7</month>
<year>2009</year>
</date>
<date date-type="accepted"><day>24</day>
<month>8</month>
<year>2009</year>
</date>
</history>
<permissions><copyright-statement>© Pfefferle et al; licensee BioMed Central Ltd. 2009</copyright-statement>
<license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p>
</license>
</permissions>
<abstract id="Abs1"><p>During the outbreak of SARS in 2002/3, a prototype virus was isolated from a patient in Frankfurt/Germany (strain Frankfurt-1). As opposed to all other SARS-Coronavirus strains, Frankfurt-1 has a 45-nucleotide deletion in the transmembrane domain of its ORF 7b protein. When over-expressed in HEK 293 cells, the full-length protein but not the variant with the deletion caused interferon beta induction and cleavage of procaspase 3. To study the role of ORF 7b in the context of virus replication, we cloned a full genome cDNA copy of Frankfurt-1 in a bacterial artificial chromosome downstream of a T7 RNA polymerase promoter. Transfection of capped RNA transcribed from this construct yielded infectious virus that was indistinguishable from the original virus isolate. The presumed Frankfurt-1 ancestor with an intact ORF 7b was reconstructed. In CaCo-2 and HUH7 cells, but not in Vero cells, the variant carrying the ORF 7b deletion had a replicative advantage against the parental virus (4- and 6-fold increase of virus RNA in supernatant, respectively). This effect was neither associated with changes in the induction or secretion of type I interferon, nor with altered induction of apoptosis in cell culture. However, pretreatment of cells with interferon beta caused the deleted virus to replicate to higher titers than the parental strain (3.4-fold in Vero cells, 7.9-fold in CaCo-2 cells).</p>
<p>In Syrian Golden Hamsters inoculated intranasally with 10e4 plaque forming units of either virus, mean titers of infectious virus and viral RNA in the lungs after 24 h were increased 23- and 94.8-fold, respectively, with the deleted virus. This difference could explain earlier observations of enhanced virulence of Frankfurt-1 in Hamsters as compared to other SARS-Coronavirus reference strains and identifies the SARS-CoV 7b protein as an attenuating factor with the SARS-Coronavirus genome. Because attenuation was focused on the early phase of infection <italic>in-vivo</italic>
, ORF 7b might have contributed to the delayed accumulation of virus in patients that was suggested to have limited the spread of the SARS epidemic.</p>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/1743-422X-6-131) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
<kwd-group xml:lang="en"><title>Keywords</title>
<kwd>Bacterial Artificial Chromosome</kwd>
<kwd>Vero Cell</kwd>
<kwd>Severe Acute Respiratory Syndrome</kwd>
<kwd>Bacterial Artificial Chromosome Clone</kwd>
<kwd>Interferon Beta</kwd>
</kwd-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2009</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Allemagne</li>
<li>États-Unis</li>
</country>
<region><li>Hambourg</li>
</region>
<settlement><li>Hambourg</li>
</settlement>
</list>
<tree><noCountry><name sortKey="Kr Hling, Verena" sort="Kr Hling, Verena" uniqKey="Kr Hling V" first="Verena" last="Kr Hling">Verena Kr Hling</name>
</noCountry>
<country name="Allemagne"><noRegion><name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</name>
</noRegion>
<name sortKey="Ditt, Vanessa" sort="Ditt, Vanessa" uniqKey="Ditt V" first="Vanessa" last="Ditt">Vanessa Ditt</name>
<name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
<name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
<name sortKey="Grywna, Klaus" sort="Grywna, Klaus" uniqKey="Grywna K" first="Klaus" last="Grywna">Klaus Grywna</name>
<name sortKey="Muhlberger, Elke" sort="Muhlberger, Elke" uniqKey="Muhlberger E" first="Elke" last="Mühlberger">Elke Mühlberger</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Muhlberger, Elke" sort="Muhlberger, Elke" uniqKey="Muhlberger E" first="Elke" last="Mühlberger">Elke Mühlberger</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Pmc/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000C81 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd -nk 000C81 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= Pmc |étape= Checkpoint |type= RBID |clé= PMC:2739521 |texte= Reverse genetic characterization of the natural genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/RBID.i -Sk "pubmed:19698190" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |