Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis
Identifieur interne : 001C50 ( Ncbi/Merge ); précédent : 001C49; suivant : 001C51Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis
Auteurs : Vineet D. Menachery [États-Unis] ; Lisa E. Gralinski [États-Unis] ; Hugh D. Mitchell [États-Unis] ; Kenneth H. Dinnon [États-Unis] ; Sarah R. Leist [États-Unis] ; Boyd L. Yount [États-Unis] ; Rachel L. Graham [États-Unis] ; Eileen T. Mcanarney [États-Unis] ; Kelly G. Stratton [États-Unis] ; Adam S. Cockrell [États-Unis] ; Kari Debbink [États-Unis] ; Amy C. Sims [États-Unis] ; Katrina M. Waters [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- mSphere [ 2379-5042 ] ; 2017.
Abstract
Coronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2′
Url:
DOI: 10.1128/mSphere.00346-17
PubMed: 29152578
PubMed Central: 5687918
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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="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E." last="Gralinski">Lisa E. 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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="Dinnon, Kenneth H" sort="Dinnon, Kenneth H" uniqKey="Dinnon K" first="Kenneth H." last="Dinnon">Kenneth H. Dinnon</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="Leist, Sarah R" sort="Leist, Sarah R" uniqKey="Leist S" first="Sarah R." last="Leist">Sarah R. Leist</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="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="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="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="Debbink, Kari" sort="Debbink, Kari" uniqKey="Debbink K" first="Kari" last="Debbink">Kari Debbink</name><affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Department of Natural Sciences, Bowie State University, Bowie, Maryland, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Natural Sciences, Bowie State University, Bowie, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C." last="Sims">Amy C. Sims</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="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">mSphere</title><idno type="eISSN">2379-5042</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Coronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2′<italic>O</italic>-MTase activity of CoVs for attenuation. With clear understanding of the IFN/IFIT (IFN-induced proteins with tetratricopeptide repeats)-based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform, as well as therapeutic development for both current and future emergent CoV strains. Importantly, other approaches targeting other conserved pan-CoV functions have not yet proven effective against MERS-CoV, illustrating the broad applicability of targeting viral 2′<italic>O</italic>-MTase function across CoVs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Vijay, R" uniqKey="Vijay R">R Vijay</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name></author><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okba, Nm" uniqKey="Okba N">NM Okba</name></author><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL 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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="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="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="Dinnon, Kenneth H" sort="Dinnon, Kenneth H" uniqKey="Dinnon K" first="Kenneth H." last="Dinnon">Kenneth H. Dinnon</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="Leist, Sarah R" sort="Leist, Sarah R" uniqKey="Leist S" first="Sarah R." last="Leist">Sarah R. Leist</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="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="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="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="Debbink, Kari" sort="Debbink, Kari" uniqKey="Debbink K" first="Kari" last="Debbink">Kari Debbink</name><affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Department of Natural Sciences, Bowie State University, Bowie, Maryland, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Natural Sciences, Bowie State University, Bowie, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C." last="Sims">Amy C. Sims</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="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></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29152578</idno><idno type="pmc">5687918</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687918</idno><idno type="RBID">PMC:5687918</idno><idno type="doi">10.1128/mSphere.00346-17</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">001252</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001252</idno><idno type="wicri:Area/Pmc/Curation">001252</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001252</idno><idno type="wicri:Area/Pmc/Checkpoint">000787</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000787</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis</title><author><name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D." last="Menachery">Vineet D. 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="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="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="Dinnon, Kenneth H" sort="Dinnon, Kenneth H" uniqKey="Dinnon K" first="Kenneth H." last="Dinnon">Kenneth H. Dinnon</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="Leist, Sarah R" sort="Leist, Sarah R" uniqKey="Leist S" first="Sarah R." last="Leist">Sarah R. Leist</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="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="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="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="Debbink, Kari" sort="Debbink, Kari" uniqKey="Debbink K" first="Kari" last="Debbink">Kari Debbink</name><affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Department of Natural Sciences, Bowie State University, Bowie, Maryland, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Natural Sciences, Bowie State University, Bowie, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C." last="Sims">Amy C. Sims</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="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">mSphere</title><idno type="eISSN">2379-5042</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Coronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2′<italic>O</italic>-MTase activity of CoVs for attenuation. With clear understanding of the IFN/IFIT (IFN-induced proteins with tetratricopeptide repeats)-based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform, as well as therapeutic development for both current and future emergent CoV strains. 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Menachery</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><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></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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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:affiliation>Pacific Northwest National Laboratory, Richland, Washington, USA.</nlm:affiliation><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="Dinnon, Kenneth H" sort="Dinnon, Kenneth H" uniqKey="Dinnon K" first="Kenneth H" last="Dinnon">Kenneth H. Dinnon</name><affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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="Leist, Sarah R" sort="Leist, Sarah R" uniqKey="Leist S" first="Sarah R" last="Leist">Sarah R. Leist</name><affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><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></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:affiliation>Pacific Northwest National Laboratory, Richland, Washington, USA.</nlm:affiliation><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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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="Debbink, Kari" sort="Debbink, Kari" uniqKey="Debbink K" first="Kari" last="Debbink">Kari Debbink</name><affiliation wicri:level="2"><nlm:affiliation>Department of Natural Sciences, Bowie State University, Bowie, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Natural Sciences, Bowie State University, Bowie, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C" last="Sims">Amy C. Sims</name><affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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="Waters, Katrina M" sort="Waters, Katrina M" uniqKey="Waters K" first="Katrina M" last="Waters">Katrina M. Waters</name><affiliation wicri:level="2"><nlm:affiliation>Pacific Northwest National Laboratory, Richland, Washington, USA.</nlm:affiliation><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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="????"><PubDate><MedlineDate>2017 Nov-Dec</MedlineDate></PubDate></date><idno type="RBID">pubmed:29152578</idno><idno type="pmid">29152578</idno><idno type="doi">10.1128/mSphere.00346-17</idno><idno type="wicri:Area/PubMed/Corpus">000A84</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000A84</idno><idno type="wicri:Area/PubMed/Curation">000A84</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000A84</idno><idno type="wicri:Area/PubMed/Checkpoint">002A12</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002A12</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis.</title><author><name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D" last="Menachery">Vineet D. Menachery</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><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></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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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:affiliation>Pacific Northwest National Laboratory, Richland, Washington, USA.</nlm:affiliation><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="Dinnon, Kenneth H" sort="Dinnon, Kenneth H" uniqKey="Dinnon K" first="Kenneth H" last="Dinnon">Kenneth H. Dinnon</name><affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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="Leist, Sarah R" sort="Leist, Sarah R" uniqKey="Leist S" first="Sarah R" last="Leist">Sarah R. Leist</name><affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><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></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:affiliation>Pacific Northwest National Laboratory, Richland, Washington, USA.</nlm:affiliation><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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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="Debbink, Kari" sort="Debbink, Kari" uniqKey="Debbink K" first="Kari" last="Debbink">Kari Debbink</name><affiliation wicri:level="2"><nlm:affiliation>Department of Natural Sciences, Bowie State University, Bowie, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Natural Sciences, Bowie State University, Bowie, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C" last="Sims">Amy C. Sims</name><affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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="Waters, Katrina M" sort="Waters, Katrina M" uniqKey="Waters K" first="Katrina M" last="Waters">Katrina M. Waters</name><affiliation wicri:level="2"><nlm:affiliation>Pacific Northwest National Laboratory, Richland, Washington, USA.</nlm:affiliation><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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><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></analytic><series><title level="j">mSphere</title><idno type="ISSN">2379-5042</idno></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2'<i>O</i>-methyltransferase (2'<i>O</i>-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis. While the absence of 2'<i>O</i>-MTase activity had only a marginal impact on propagation and replication in Vero cells, dNSP16 mutant MERS-CoV demonstrated significant attenuation relative to the control both in primary human airway cell cultures and <i>in vivo</i>. Further examination indicated that dNSP16 mutant MERS-CoV had a type I interferon (IFN)-based attenuation and was partially restored in the absence of molecules of IFN-induced proteins with tetratricopeptide repeats. Importantly, the robust attenuation permitted the use of dNSP16 mutant MERS-CoV as a live attenuated vaccine platform protecting from a challenge with a mouse-adapted MERS-CoV strain. These studies demonstrate the importance of the conserved 2'<i>O</i>-MTase activity for CoV pathogenesis and highlight NSP16 as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting. <b>IMPORTANCE</b> Coronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2'<i>O</i>-MTase activity of CoVs for attenuation. With clear understanding of the IFN/IFIT (IFN-induced proteins with tetratricopeptide repeats)-based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform, as well as therapeutic development for both current and future emergent CoV strains. Importantly, other approaches targeting other conserved pan-CoV functions have not yet proven effective against MERS-CoV, illustrating the broad applicability of targeting viral 2'<i>O</i>-MTase function across CoVs.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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