Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets
Identifieur interne : 001671 ( Main/Exploration ); précédent : 001670; suivant : 001672Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets
Auteurs : Yang Yang [République populaire de Chine] ; Fei Ye [République populaire de Chine] ; Na Zhu [République populaire de Chine] ; Wenling Wang [République populaire de Chine] ; Yao Deng [République populaire de Chine] ; Zhengdong Zhao [République populaire de Chine] ; Wenjie Tan [République populaire de Chine]Source :
- Scientific Reports [ 2045-2322 ] ; 2015.
Descripteurs français
- KwdFr :
- Cellules HeLa (virologie), Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Cytoplasme (métabolisme), Cytoplasme (virologie), Facteur-3 de régulation d'interféron (génétique), Facteur-3 de régulation d'interféron (métabolisme), Facteur-7 de régulation d'interféron (métabolisme), Humains, Hélicase IFIH1 inductrice de l'interféron (génétique), Hélicase IFIH1 inductrice de l'interféron (métabolisme), I-kappa B Kinase (métabolisme), Interactions hôte-pathogène, Interféron bêta (génétique), Interféron bêta (métabolisme), Noyau de la cellule (métabolisme), Noyau de la cellule (virologie), Phosphorylation, Protein-Serine-Threonine Kinases (métabolisme), Protéine-58 à domaine DEAD (génétique), Protéine-58 à domaine DEAD (métabolisme), Protéines adaptatrices de la transduction du signal (métabolisme), Protéines virales (génétique), Protéines virales (métabolisme), Protéines virales (pharmacologie).
- MESH :
- génétique : Facteur-3 de régulation d'interféron, Hélicase IFIH1 inductrice de l'interféron, Interféron bêta, Protéine-58 à domaine DEAD, Protéines virales.
- métabolisme : Cytoplasme, Facteur-3 de régulation d'interféron, Facteur-7 de régulation d'interféron, Hélicase IFIH1 inductrice de l'interféron, I-kappa B Kinase, Interféron bêta, Noyau de la cellule, Protein-Serine-Threonine Kinases, Protéine-58 à domaine DEAD, Protéines adaptatrices de la transduction du signal, Protéines virales.
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- pharmacologie : Protéines virales.
- virologie : Cellules HeLa, Cytoplasme, Noyau de la cellule.
- Humains, Interactions hôte-pathogène, Phosphorylation.
English descriptors
- KwdEn :
- Adaptor Proteins, Signal Transducing (metabolism), Cell Nucleus (metabolism), Cell Nucleus (virology), Cytoplasm (metabolism), Cytoplasm (virology), DEAD Box Protein 58 (genetics), DEAD Box Protein 58 (metabolism), HeLa Cells (virology), Host-Pathogen Interactions, Humans, I-kappa B Kinase (metabolism), Interferon Regulatory Factor-3 (genetics), Interferon Regulatory Factor-3 (metabolism), Interferon Regulatory Factor-7 (metabolism), Interferon-Induced Helicase, IFIH1 (genetics), Interferon-Induced Helicase, IFIH1 (metabolism), Interferon-beta (genetics), Interferon-beta (metabolism), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Phosphorylation, Protein-Serine-Threonine Kinases (metabolism), Viral Proteins (genetics), Viral Proteins (metabolism), Viral Proteins (pharmacology).
- MESH :
- chemical , genetics : DEAD Box Protein 58, Interferon Regulatory Factor-3, Interferon-Induced Helicase, IFIH1, Interferon-beta, Viral Proteins.
- chemical , metabolism : Adaptor Proteins, Signal Transducing, DEAD Box Protein 58, I-kappa B Kinase, Interferon Regulatory Factor-3, Interferon Regulatory Factor-7, Interferon-Induced Helicase, IFIH1, Interferon-beta, Protein-Serine-Threonine Kinases, Viral Proteins.
- metabolism : Cell Nucleus, Cytoplasm.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- chemical , pharmacology : Viral Proteins.
- virology : Cell Nucleus, Cytoplasm, HeLa Cells.
- Host-Pathogen Interactions, Humans, Phosphorylation.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel and highly pathogenic human coronavirus and has quickly spread to other countries in the Middle East, Europe, North Africa and Asia since 2012. Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. Further analysis showed that ORF4b could also inhibit IRF3 and IRF7-induced production of IFN-β, whereas deletion of the nuclear localization signal of ORF4b abrogated its ability to inhibit IRF3 and IRF7-induced production of IFN-β, but not IFN-β production induced by RIG-I, MDA5, MAVS, IKKε and TBK-1, suggesting that ORF4b could inhibit the induction of IFN-β in both the cytoplasm and nucleus. Collectively, these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm and also in the nucleus with unknown mechanism. Viruses have evolved multiple strategies to evade or thwart a host’s antiviral responses. A novel human coronavirus (HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV), is distinguished from other coronaviruses by its high pathogenicity and mortality. However, virulence determinants that distinguish MERS-CoV from other HCoVs have yet to be identified. MERS-CoV ORF4b antagonizes the early antiviral response, which may contribute to MERS-CoV pathogenesis. Here, we report the identification of the interferon (IFN) antagonism mechanism of MERS-CoV ORF4b. MERS-CoV ORF4b inhibits the production of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm and also in the nucleus with unknown mechanism. These findings provide a rationale for the novel pathogenesis of MERS-CoV as well as a basis for developing a candidate therapeutic against this virus.
Url:
DOI: 10.1038/srep17554
PubMed: 26631542
PubMed Central: 4668369
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000428
- to stream Pmc, to step Curation: 000428
- to stream Pmc, to step Checkpoint: 000D71
- to stream PubMed, to step Corpus: 001360
- to stream PubMed, to step Curation: 001360
- to stream PubMed, to step Checkpoint: 001445
- to stream Ncbi, to step Merge: 001382
- to stream Ncbi, to step Curation: 001382
- to stream Ncbi, to step Checkpoint: 001382
- to stream Main, to step Merge: 001676
- to stream Main, to step Curation: 001671
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets</title>
<author><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.410741.7</institution-id>
<institution>Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People’s Hospital,</institution>
</institution-wrap>
Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shenzhen</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ye, Fei" sort="Ye, Fei" uniqKey="Ye F" first="Fei" last="Ye">Fei Ye</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhu, Na" sort="Zhu, Na" uniqKey="Zhu N" first="Na" last="Zhu">Na Zhu</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wang, Wenling" sort="Wang, Wenling" uniqKey="Wang W" first="Wenling" last="Wang">Wenling Wang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Deng, Yao" sort="Deng, Yao" uniqKey="Deng Y" first="Yao" last="Deng">Yao Deng</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhao, Zhengdong" sort="Zhao, Zhengdong" uniqKey="Zhao Z" first="Zhengdong" last="Zhao">Zhengdong Zhao</name>
<affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Pathogen System Biology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 100176 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.410318.f</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0632 3409</institution-id>
<institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences,</institution>
</institution-wrap>
Beijing, 100176 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">26631542</idno>
<idno type="pmc">4668369</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668369</idno>
<idno type="RBID">PMC:4668369</idno>
<idno type="doi">10.1038/srep17554</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000428</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000428</idno>
<idno type="wicri:Area/Pmc/Curation">000428</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000428</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000D71</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000D71</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="RBID">pubmed:26631542</idno>
<idno type="wicri:Area/PubMed/Corpus">001360</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001360</idno>
<idno type="wicri:Area/PubMed/Curation">001360</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001360</idno>
<idno type="wicri:Area/PubMed/Checkpoint">001445</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001445</idno>
<idno type="wicri:Area/Ncbi/Merge">001382</idno>
<idno type="wicri:Area/Ncbi/Curation">001382</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">001382</idno>
<idno type="wicri:Area/Main/Merge">001676</idno>
<idno type="wicri:Area/Main/Curation">001671</idno>
<idno type="wicri:Area/Main/Exploration">001671</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets</title>
<author><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.410741.7</institution-id>
<institution>Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People’s Hospital,</institution>
</institution-wrap>
Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shenzhen</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ye, Fei" sort="Ye, Fei" uniqKey="Ye F" first="Fei" last="Ye">Fei Ye</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhu, Na" sort="Zhu, Na" uniqKey="Zhu N" first="Na" last="Zhu">Na Zhu</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wang, Wenling" sort="Wang, Wenling" uniqKey="Wang W" first="Wenling" last="Wang">Wenling Wang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Deng, Yao" sort="Deng, Yao" uniqKey="Deng Y" first="Yao" last="Deng">Yao Deng</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhao, Zhengdong" sort="Zhao, Zhengdong" uniqKey="Zhao Z" first="Zhengdong" last="Zhao">Zhengdong Zhao</name>
<affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Pathogen System Biology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 100176 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.410318.f</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0632 3409</institution-id>
<institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences,</institution>
</institution-wrap>
Beijing, 100176 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.453135.5</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1769 3691</institution-id>
<institution>Key Laboratory of Medical Virology, Ministry of Health,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Scientific Reports</title>
<idno type="eISSN">2045-2322</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptor Proteins, Signal Transducing (metabolism)</term>
<term>Cell Nucleus (metabolism)</term>
<term>Cell Nucleus (virology)</term>
<term>Cytoplasm (metabolism)</term>
<term>Cytoplasm (virology)</term>
<term>DEAD Box Protein 58 (genetics)</term>
<term>DEAD Box Protein 58 (metabolism)</term>
<term>HeLa Cells (virology)</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>I-kappa B Kinase (metabolism)</term>
<term>Interferon Regulatory Factor-3 (genetics)</term>
<term>Interferon Regulatory Factor-3 (metabolism)</term>
<term>Interferon Regulatory Factor-7 (metabolism)</term>
<term>Interferon-Induced Helicase, IFIH1 (genetics)</term>
<term>Interferon-Induced Helicase, IFIH1 (metabolism)</term>
<term>Interferon-beta (genetics)</term>
<term>Interferon-beta (metabolism)</term>
<term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term>
<term>Phosphorylation</term>
<term>Protein-Serine-Threonine Kinases (metabolism)</term>
<term>Viral Proteins (genetics)</term>
<term>Viral Proteins (metabolism)</term>
<term>Viral Proteins (pharmacology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Cellules HeLa (virologie)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term>
<term>Cytoplasme (métabolisme)</term>
<term>Cytoplasme (virologie)</term>
<term>Facteur-3 de régulation d'interféron (génétique)</term>
<term>Facteur-3 de régulation d'interféron (métabolisme)</term>
<term>Facteur-7 de régulation d'interféron (métabolisme)</term>
<term>Humains</term>
<term>Hélicase IFIH1 inductrice de l'interféron (génétique)</term>
<term>Hélicase IFIH1 inductrice de l'interféron (métabolisme)</term>
<term>I-kappa B Kinase (métabolisme)</term>
<term>Interactions hôte-pathogène</term>
<term>Interféron bêta (génétique)</term>
<term>Interféron bêta (métabolisme)</term>
<term>Noyau de la cellule (métabolisme)</term>
<term>Noyau de la cellule (virologie)</term>
<term>Phosphorylation</term>
<term>Protein-Serine-Threonine Kinases (métabolisme)</term>
<term>Protéine-58 à domaine DEAD (génétique)</term>
<term>Protéine-58 à domaine DEAD (métabolisme)</term>
<term>Protéines adaptatrices de la transduction du signal (métabolisme)</term>
<term>Protéines virales (génétique)</term>
<term>Protéines virales (métabolisme)</term>
<term>Protéines virales (pharmacologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DEAD Box Protein 58</term>
<term>Interferon Regulatory Factor-3</term>
<term>Interferon-Induced Helicase, IFIH1</term>
<term>Interferon-beta</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term>
<term>DEAD Box Protein 58</term>
<term>I-kappa B Kinase</term>
<term>Interferon Regulatory Factor-3</term>
<term>Interferon Regulatory Factor-7</term>
<term>Interferon-Induced Helicase, IFIH1</term>
<term>Interferon-beta</term>
<term>Protein-Serine-Threonine Kinases</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur-3 de régulation d'interféron</term>
<term>Hélicase IFIH1 inductrice de l'interféron</term>
<term>Interféron bêta</term>
<term>Protéine-58 à domaine DEAD</term>
<term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cell Nucleus</term>
<term>Cytoplasm</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cytoplasme</term>
<term>Facteur-3 de régulation d'interféron</term>
<term>Facteur-7 de régulation d'interféron</term>
<term>Hélicase IFIH1 inductrice de l'interféron</term>
<term>I-kappa B Kinase</term>
<term>Interféron bêta</term>
<term>Noyau de la cellule</term>
<term>Protein-Serine-Threonine Kinases</term>
<term>Protéine-58 à domaine DEAD</term>
<term>Protéines adaptatrices de la transduction du signal</term>
<term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Cellules HeLa</term>
<term>Cytoplasme</term>
<term>Noyau de la cellule</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Cell Nucleus</term>
<term>Cytoplasm</term>
<term>HeLa Cells</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Phosphorylation</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Humains</term>
<term>Interactions hôte-pathogène</term>
<term>Phosphorylation</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel and highly pathogenic human coronavirus and has quickly spread to other countries in the Middle East, Europe, North Africa and Asia since 2012. Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. Further analysis showed that ORF4b could also inhibit IRF3 and IRF7-induced production of IFN-β, whereas deletion of the nuclear localization signal of ORF4b abrogated its ability to inhibit IRF3 and IRF7-induced production of IFN-β, but not IFN-β production induced by RIG-I, MDA5, MAVS, IKKε and TBK-1, suggesting that ORF4b could inhibit the induction of IFN-β in both the cytoplasm and nucleus. Collectively, these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm and also in the nucleus with unknown mechanism. Viruses have evolved multiple strategies to evade or thwart a host’s antiviral responses. A novel human coronavirus (HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV), is distinguished from other coronaviruses by its high pathogenicity and mortality. However, virulence determinants that distinguish MERS-CoV from other HCoVs have yet to be identified. MERS-CoV ORF4b antagonizes the early antiviral response, which may contribute to MERS-CoV pathogenesis. Here, we report the identification of the interferon (IFN) antagonism mechanism of MERS-CoV ORF4b. MERS-CoV ORF4b inhibits the production of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm and also in the nucleus with unknown mechanism. These findings provide a rationale for the novel pathogenesis of MERS-CoV as well as a basis for developing a candidate therapeutic against this virus.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name>
</author>
<author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name>
</author>
<author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name>
</author>
<author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name>
</author>
<author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Butler, D" uniqKey="Butler D">D Butler</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Breban, R" uniqKey="Breban R">R Breban</name>
</author>
<author><name sortKey="Riou, J" uniqKey="Riou J">J Riou</name>
</author>
<author><name sortKey="Fontanet, A" uniqKey="Fontanet A">A Fontanet</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name>
</author>
<author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name>
</author>
<author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name>
</author>
</analytic>
</biblStruct>
<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 Stöhr</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A García-Sastre</name>
</author>
<author><name sortKey="Biron, Ca" uniqKey="Biron C">CA Biron</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Randall, Re" uniqKey="Randall R">RE Randall</name>
</author>
<author><name sortKey="Goodbourn, S" uniqKey="Goodbourn S">S Goodbourn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bermingham, A" uniqKey="Bermingham A">A Bermingham</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zielecki, F" uniqKey="Zielecki F">F Zielecki</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chan, Rw" uniqKey="Chan R">RW Chan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="De Wilde, Ah" uniqKey="De Wilde A">AH de Wilde</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Niemeyer, D" uniqKey="Niemeyer D">D Niemeyer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Matthews, Kl" uniqKey="Matthews K">KL Matthews</name>
</author>
<author><name sortKey="Coleman, Cm" uniqKey="Coleman C">CM Coleman</name>
</author>
<author><name sortKey="Van Der Meer, Y" uniqKey="Van Der Meer Y">Y van der Meer</name>
</author>
<author><name sortKey="Snijder, Ej" uniqKey="Snijder E">EJ Snijder</name>
</author>
<author><name sortKey="Frieman, Mb" uniqKey="Frieman M">MB Frieman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Siu, Kl" uniqKey="Siu K">KL Siu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yang, X" uniqKey="Yang X">X Yang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bailey Elkin, Ba" uniqKey="Bailey Elkin B">BA Bailey-Elkin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Takeuchi, O" uniqKey="Takeuchi O">O Takeuchi</name>
</author>
<author><name sortKey="Akira, S" uniqKey="Akira S">S Akira</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Seth, Rb" uniqKey="Seth R">RB Seth</name>
</author>
<author><name sortKey="Sun, L" uniqKey="Sun L">L Sun</name>
</author>
<author><name sortKey="Ea, Ck" uniqKey="Ea C">CK Ea</name>
</author>
<author><name sortKey="Chen, Zj" uniqKey="Chen Z">ZJ Chen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Meylan, E" uniqKey="Meylan E">E Meylan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kawai, T" uniqKey="Kawai T">T Kawai</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Scobey, T" uniqKey="Scobey T">T Scobey</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Almazan, F" uniqKey="Almazan F">F Almazán</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Khan, S" uniqKey="Khan S">S Khan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Childs, Ks" uniqKey="Childs K">KS Childs</name>
</author>
<author><name sortKey="Andrejeva, J" uniqKey="Andrejeva J">J Andrejeva</name>
</author>
<author><name sortKey="Randall, Re" uniqKey="Randall R">RE Randall</name>
</author>
<author><name sortKey="Goodbourn, S" uniqKey="Goodbourn S">S Goodbourn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Prins, Kc" uniqKey="Prins K">KC Prins</name>
</author>
<author><name sortKey="Cardenas, Wb" uniqKey="Cardenas W">WB Cardenas</name>
</author>
<author><name sortKey="Basler, Cf" uniqKey="Basler C">CF Basler</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Taylor, Ke" uniqKey="Taylor K">KE Taylor</name>
</author>
<author><name sortKey="Mossman, Kl" uniqKey="Mossman K">KL Mossman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Totura, Al" uniqKey="Totura A">AL Totura</name>
</author>
<author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</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="Devaraj, Sg" uniqKey="Devaraj S">SG Devaraj</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Frieman, M" uniqKey="Frieman M">M Frieman</name>
</author>
<author><name sortKey="Ratia, K" uniqKey="Ratia K">K Ratia</name>
</author>
<author><name sortKey="Johnston, Re" uniqKey="Johnston R">RE Johnston</name>
</author>
<author><name sortKey="Mesecar, Ad" uniqKey="Mesecar A">AD Mesecar</name>
</author>
<author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Clementz, Ma" uniqKey="Clementz M">MA Clementz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wathelet, Mg" uniqKey="Wathelet M">MG Wathelet</name>
</author>
<author><name sortKey="Orr, M" uniqKey="Orr M">M Orr</name>
</author>
<author><name sortKey="Frieman, Mb" uniqKey="Frieman M">MB Frieman</name>
</author>
<author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Narayanan, K" uniqKey="Narayanan K">K Narayanan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zust, R" uniqKey="Zust R">R Zust</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Siu, Kl" uniqKey="Siu K">KL Siu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shi, Cs" uniqKey="Shi C">CS Shi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kaukinen, P" uniqKey="Kaukinen P">P Kaukinen</name>
</author>
<author><name sortKey="Sillanp, M" uniqKey="Sillanp M">M Sillanpää</name>
</author>
<author><name sortKey="Nousiainen, L" uniqKey="Nousiainen L">L Nousiainen</name>
</author>
<author><name sortKey="Melen, K" uniqKey="Melen K">K Melén</name>
</author>
<author><name sortKey="Julkunen, I" uniqKey="Julkunen I">I Julkunen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lu, Ll" uniqKey="Lu L">LL Lu</name>
</author>
<author><name sortKey="Puri, M" uniqKey="Puri M">M Puri</name>
</author>
<author><name sortKey="Horvath, Cm" uniqKey="Horvath C">CM Horvath</name>
</author>
<author><name sortKey="Sen, Gc" uniqKey="Sen G">GC Sen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brz Zka, K" uniqKey="Brz Zka K">K Brzózka</name>
</author>
<author><name sortKey="Finke, S" uniqKey="Finke S">S Finke</name>
</author>
<author><name sortKey="Conzelmann, Kk" uniqKey="Conzelmann K">KK Conzelmann</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ren, J" uniqKey="Ren J">J Ren</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Le May, N" uniqKey="Le May N">N Le May</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rodriguez, A" uniqKey="Rodriguez A">A Rodriguez</name>
</author>
<author><name sortKey="Perez Gonzalez, A" uniqKey="Perez Gonzalez A">A Pérez-González</name>
</author>
<author><name sortKey="Nieto, A" uniqKey="Nieto A">A Nieto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Llompart, Cm" uniqKey="Llompart C">CM Llompart</name>
</author>
<author><name sortKey="Nieto, A" uniqKey="Nieto A">A Nieto</name>
</author>
<author><name sortKey="Rodriguez Frandsen, A" uniqKey="Rodriguez Frandsen A">A Rodriguez-Frandsen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rodriguez, A" uniqKey="Rodriguez A">A Rodriguez</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dai Ju, Jq" uniqKey="Dai Ju J">JQ Dai-Ju</name>
</author>
<author><name sortKey="Li, L" uniqKey="Li L">L Li</name>
</author>
<author><name sortKey="Johnson, La" uniqKey="Johnson L">LA Johnson</name>
</author>
<author><name sortKey="Sandri Goldin, Rm" uniqKey="Sandri Goldin R">RM Sandri-Goldin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fraser, Ka" uniqKey="Fraser K">KA Fraser</name>
</author>
<author><name sortKey="Rice, Sa" uniqKey="Rice S">SA Rice</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Leonard, Vh" uniqKey="Leonard V">VH Léonard</name>
</author>
<author><name sortKey="Kohl, A" uniqKey="Kohl A">A Kohl</name>
</author>
<author><name sortKey="Hart, Tj" uniqKey="Hart T">TJ Hart</name>
</author>
<author><name sortKey="Elliott, Rm" uniqKey="Elliott R">RM Elliott</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zaborowska, J" uniqKey="Zaborowska J">J Zaborowska</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wolff, T" uniqKey="Wolff T">T Wolff</name>
</author>
<author><name sortKey="Ludwig, S" uniqKey="Ludwig S">S Ludwig</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Engel, Da" uniqKey="Engel D">DA Engel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gack, Mu" uniqKey="Gack M">MU Gack</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Noah, Dl" uniqKey="Noah D">DL Noah</name>
</author>
<author><name sortKey="Twu, Ky" uniqKey="Twu K">KY Twu</name>
</author>
<author><name sortKey="Krug, Rm" uniqKey="Krug R">RM Krug</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Satterly, N" uniqKey="Satterly N">N Satterly</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kochs, G" uniqKey="Kochs G">G Kochs</name>
</author>
<author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A García-Sastre</name>
</author>
<author><name sortKey="Martinez Sobrido, L" uniqKey="Martinez Sobrido L">L Martínez-Sobrido</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wang, B" uniqKey="Wang B">B Wang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lei, X" uniqKey="Lei X">X Lei</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
</country>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name>
</noRegion>
<name sortKey="Deng, Yao" sort="Deng, Yao" uniqKey="Deng Y" first="Yao" last="Deng">Yao Deng</name>
<name sortKey="Deng, Yao" sort="Deng, Yao" uniqKey="Deng Y" first="Yao" last="Deng">Yao Deng</name>
<name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name>
<name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name>
<name sortKey="Wang, Wenling" sort="Wang, Wenling" uniqKey="Wang W" first="Wenling" last="Wang">Wenling Wang</name>
<name sortKey="Wang, Wenling" sort="Wang, Wenling" uniqKey="Wang W" first="Wenling" last="Wang">Wenling Wang</name>
<name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name>
<name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name>
<name sortKey="Ye, Fei" sort="Ye, Fei" uniqKey="Ye F" first="Fei" last="Ye">Fei Ye</name>
<name sortKey="Ye, Fei" sort="Ye, Fei" uniqKey="Ye F" first="Fei" last="Ye">Fei Ye</name>
<name sortKey="Zhao, Zhengdong" sort="Zhao, Zhengdong" uniqKey="Zhao Z" first="Zhengdong" last="Zhao">Zhengdong Zhao</name>
<name sortKey="Zhao, Zhengdong" sort="Zhao, Zhengdong" uniqKey="Zhao Z" first="Zhengdong" last="Zhao">Zhengdong Zhao</name>
<name sortKey="Zhu, Na" sort="Zhu, Na" uniqKey="Zhu N" first="Na" last="Zhu">Na Zhu</name>
<name sortKey="Zhu, Na" sort="Zhu, Na" uniqKey="Zhu N" first="Na" last="Zhu">Na Zhu</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001671 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001671 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= MersV1 |flux= Main |étape= Exploration |type= RBID |clé= PMC:4668369 |texte= Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:26631542" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \ | NlmPubMed2Wicri -a MersV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |