MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis
Identifieur interne : 000804 ( Pmc/Checkpoint ); précédent : 000803; suivant : 000805MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis
Auteurs : Vineet D. Menachery [États-Unis] ; Hugh D. Mitchell [États-Unis] ; Adam S. Cockrell [États-Unis] ; Lisa E. Gralinski [États-Unis] ; Boyd L. Yount [États-Unis] ; Rachel L. Graham [États-Unis] ; Eileen T. Mcanarney [États-Unis] ; Madeline G. Douglas [États-Unis] ; Trevor Scobey [États-Unis] ; Anne Beall [États-Unis] ; Kenneth Dinnon [États-Unis] ; Jacob F. Kocher [États-Unis] ; Andrew E. Hale [États-Unis] ; Kelly G. Stratton [États-Unis] ; Katrina M. Waters [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- mBio [ 2150-7511 ] ; 2017.
Abstract
While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation.
Url:
DOI: 10.1128/mBio.00665-17
PubMed: 28830941
PubMed Central: 5565963
Affiliations:
- États-Unis
- Caroline du Nord, Texas, Washington (État)
- Chapel Hill (Caroline du Nord)
- Université de Caroline du Nord à Chapel Hill
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PMC:5565963Le document en format XML
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Menachery</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Mitchell, Hugh D" sort="Mitchell, Hugh D" uniqKey="Mitchell H" first="Hugh D." last="Mitchell">Hugh D. Mitchell</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Pacific Northwest National Laboratory, Richland, Washington, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Pacific Northwest National Laboratory, Richland, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Cockrell, Adam S" sort="Cockrell, Adam S" uniqKey="Cockrell A" first="Adam S." last="Cockrell">Adam S. Cockrell</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E." last="Gralinski">Lisa E. Gralinski</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Yount, Boyd L" sort="Yount, Boyd L" uniqKey="Yount B" first="Boyd L." last="Yount">Boyd L. Yount</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L." last="Graham">Rachel L. Graham</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Mcanarney, Eileen T" sort="Mcanarney, Eileen T" uniqKey="Mcanarney E" first="Eileen T." last="Mcanarney">Eileen T. Mcanarney</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Douglas, Madeline G" sort="Douglas, Madeline G" uniqKey="Douglas M" first="Madeline G." last="Douglas">Madeline G. Douglas</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Scobey, Trevor" sort="Scobey, Trevor" uniqKey="Scobey T" first="Trevor" last="Scobey">Trevor Scobey</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Beall, Anne" sort="Beall, Anne" uniqKey="Beall A" first="Anne" last="Beall">Anne Beall</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Dinnon, Kenneth" sort="Dinnon, Kenneth" uniqKey="Dinnon K" first="Kenneth" last="Dinnon">Kenneth Dinnon</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Kocher, Jacob F" sort="Kocher, Jacob F" uniqKey="Kocher J" first="Jacob F." last="Kocher">Jacob F. Kocher</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Hale, Andrew E" sort="Hale, Andrew E" uniqKey="Hale A" first="Andrew E." last="Hale">Andrew E. Hale</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Stratton, Kelly G" sort="Stratton, Kelly G" uniqKey="Stratton K" first="Kelly G." last="Stratton">Kelly G. Stratton</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Pacific Northwest National Laboratory, Richland, Washington, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Pacific Northwest National Laboratory, Richland, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Waters, Katrina M" sort="Waters, Katrina M" uniqKey="Waters K" first="Katrina M." last="Waters">Katrina M. Waters</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Pacific Northwest National Laboratory, Richland, Washington, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Pacific Northwest National Laboratory, Richland, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author></analytic><series><title level="j">mBio</title><idno type="eISSN">2150-7511</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><p>While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation. <italic>In vitro</italic> replication attenuation also extends to <italic>in vivo</italic> models, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">mBio</journal-id><journal-id journal-id-type="iso-abbrev">MBio</journal-id><journal-id journal-id-type="hwp">mbio</journal-id><journal-id journal-id-type="pmc">mbio</journal-id><journal-id journal-id-type="publisher-id">mBio</journal-id><journal-title-group><journal-title>mBio</journal-title></journal-title-group><issn pub-type="epub">2150-7511</issn><publisher><publisher-name>American Society for Microbiology</publisher-name><publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28830941</article-id><article-id pub-id-type="pmc">5565963</article-id><article-id pub-id-type="publisher-id">mBio00665-17</article-id><article-id pub-id-type="doi">10.1128/mBio.00665-17</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis</article-title><alt-title alt-title-type="running-head">MERS-CoV Accessory ORFs Are Key for Pathogenesis</alt-title><alt-title alt-title-type="short-authors">Menachery et al.</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Menachery</surname><given-names>Vineet D.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mitchell</surname><given-names>Hugh D.</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cockrell</surname><given-names>Adam S.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gralinski</surname><given-names>Lisa E.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yount</surname><given-names>Boyd L.</given-names><suffix>Jr.</suffix></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Graham</surname><given-names>Rachel L.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>McAnarney</surname><given-names>Eileen T.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Douglas</surname><given-names>Madeline G.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Scobey</surname><given-names>Trevor</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Beall</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dinnon</surname><given-names>Kenneth</given-names><suffix>III</suffix></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kocher</surname><given-names>Jacob F.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hale</surname><given-names>Andrew E.</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stratton</surname><given-names>Kelly G.</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Waters</surname><given-names>Katrina M.</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Baric</surname><given-names>Ralph S.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><aff id="aff1"><label>a</label><addr-line>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA</addr-line></aff><aff id="aff2"><label>b</label><addr-line>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></aff><aff id="aff3"><label>c</label><addr-line>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</addr-line></aff><aff id="aff4"><label>d</label><addr-line>Pacific Northwest National Laboratory, Richland, Washington, USA</addr-line></aff></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Racaniello</surname><given-names>Vincent R.</given-names></name><role>Editor</role><aff>Columbia University College of Physicians & Surgeons</aff></contrib></contrib-group><author-notes><corresp id="cor1">Address correspondence to Ralph S. Baric, <email>Rbaric@email.unc.edu</email>.</corresp></author-notes><pub-date pub-type="epub"><day>22</day><month>8</month><year>2017</year></pub-date><pub-date pub-type="collection"><season>Jul-Aug</season><year>2017</year></pub-date><volume>8</volume><issue>4</issue><elocation-id>e00665-17</elocation-id><history><date date-type="received"><day>27</day><month>4</month><year>2017</year></date><date date-type="accepted"><day>17</day><month>7</month><year>2017</year></date></history><permissions><copyright-statement>Copyright © 2017 Menachery et al.</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>Menachery et al.</copyright-holder><license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="mbo004173446001.pdf"></self-uri><abstract><title>ABSTRACT</title><p>While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation. <italic>In vitro</italic> replication attenuation also extends to <italic>in vivo</italic> models, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward.</p></abstract><abstract abstract-type="executive-summary"><title>IMPORTANCE</title><p>The initial emergence and periodic outbreaks of MERS-CoV highlight a continuing threat posed by zoonotic pathogens to global public health. In these studies, mutant virus generation demonstrates the necessity of accessory ORFs in regard to MERS-CoV infection and pathogenesis. With this in mind, accessory ORF functions can be targeted for both therapeutic and vaccine treatments in response to MERS-CoV and related group 2C coronaviruses. In addition, disruption of accessory ORFs in parallel may offer a rapid response platform to attenuation of future emergent strains based on both SARS- and MERS-CoV accessory ORF mutants.</p></abstract><kwd-group><title>KEYWORDS</title><kwd>coronavirus</kwd><kwd>MERS-CoV</kwd><kwd>SARS-CoV</kwd><kwd>live vector vaccines</kwd><kwd>reverse genetics</kwd></kwd-group><funding-group><award-group id="award1"><funding-source>HHS | National Institutes of Health (NIH)
<named-content content-type="funder-id">https://doi.org/10.13039/100000002</named-content></funding-source><award-id>K99AG049092</award-id><principal-award-recipient>Vineet D. Menachery</principal-award-recipient></award-group><award-group id="award2"><funding-source>HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
<named-content content-type="funder-id">https://doi.org/10.13039/100000060</named-content></funding-source><award-id>U19AI100625</award-id><award-id>U19AI106772</award-id><award-id>HHSN272201000019I-HHSN27200003</award-id><principal-award-recipient>Ralph S. Baric</principal-award-recipient></award-group></funding-group><counts><count count="3" count-type="supplementary-material"></count><fig-count count="6"></fig-count><table-count count="0"></table-count><equation-count count="0"></equation-count><ref-count count="42"></ref-count><page-count count="14"></page-count><word-count count="7499"></word-count></counts><custom-meta-group><custom-meta><meta-name>cover-date</meta-name><meta-value>July/August 2017</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Texas</li><li>Washington (État)</li></region><settlement><li>Chapel Hill (Caroline du Nord)</li></settlement><orgName><li>Université de Caroline du Nord à Chapel Hill</li></orgName></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D." last="Menachery">Vineet D. Menachery</name></region><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Beall, Anne" sort="Beall, Anne" uniqKey="Beall A" first="Anne" last="Beall">Anne Beall</name><name sortKey="Cockrell, Adam S" sort="Cockrell, Adam S" uniqKey="Cockrell A" first="Adam S." last="Cockrell">Adam S. Cockrell</name><name sortKey="Dinnon, Kenneth" sort="Dinnon, Kenneth" uniqKey="Dinnon K" first="Kenneth" last="Dinnon">Kenneth Dinnon</name><name sortKey="Douglas, Madeline G" sort="Douglas, Madeline G" uniqKey="Douglas M" first="Madeline G." last="Douglas">Madeline G. Douglas</name><name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L." last="Graham">Rachel L. Graham</name><name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E." last="Gralinski">Lisa E. Gralinski</name><name sortKey="Hale, Andrew E" sort="Hale, Andrew E" uniqKey="Hale A" first="Andrew E." last="Hale">Andrew E. Hale</name><name sortKey="Kocher, Jacob F" sort="Kocher, Jacob F" uniqKey="Kocher J" first="Jacob F." last="Kocher">Jacob F. Kocher</name><name sortKey="Mcanarney, Eileen T" sort="Mcanarney, Eileen T" uniqKey="Mcanarney E" first="Eileen T." last="Mcanarney">Eileen T. Mcanarney</name><name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D." last="Menachery">Vineet D. Menachery</name><name sortKey="Mitchell, Hugh D" sort="Mitchell, Hugh D" uniqKey="Mitchell H" first="Hugh D." last="Mitchell">Hugh D. Mitchell</name><name sortKey="Scobey, Trevor" sort="Scobey, Trevor" uniqKey="Scobey T" first="Trevor" last="Scobey">Trevor Scobey</name><name sortKey="Stratton, Kelly G" sort="Stratton, Kelly G" uniqKey="Stratton K" first="Kelly G." last="Stratton">Kelly G. Stratton</name><name sortKey="Waters, Katrina M" sort="Waters, Katrina M" uniqKey="Waters K" first="Katrina M." last="Waters">Katrina M. Waters</name><name sortKey="Yount, Boyd L" sort="Yount, Boyd L" uniqKey="Yount B" first="Boyd L." last="Yount">Boyd L. Yount</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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