Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication.
Identifieur interne : 000E47 ( Main/Exploration ); précédent : 000E46; suivant : 000E48Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication.
Auteurs : Eveline Kindler [Suisse] ; Cristina Gil-Cruz [Suisse] ; Julia Spanier [Allemagne] ; Yize Li [États-Unis] ; Jochen Wilhelm [Allemagne] ; Huib H. Rabouw [Pays-Bas] ; Roland Züst [Singapour] ; Mihyun Hwang [États-Unis] ; Philip V'Kovski [Suisse] ; Hanspeter Stalder [Suisse] ; Sabrina Marti [Suisse] ; Matthias Habjan [Allemagne] ; Luisa Cervantes-Barragan [États-Unis] ; Ruth Elliot [États-Unis] ; Nadja Karl [Allemagne] ; Christina Gaughan [États-Unis] ; Frank J M. Van Kuppeveld [Pays-Bas] ; Robert H. Silverman [États-Unis] ; Markus Keller [Allemagne] ; Burkhard Ludewig [Suisse] ; Cornelia C. Bergmann [États-Unis] ; John Ziebuhr [Allemagne] ; Susan R. Weiss [États-Unis] ; Ulrich Kalinke [Allemagne] ; Volker Thiel [Suisse]Source :
- PLoS pathogens [ 1553-7374 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux, Coronaviridae (enzymologie), Coronaviridae (immunologie), Cytométrie en flux, Endonucleases (immunologie), Humains, Immunité innée (immunologie), Infections à coronavirus (immunologie), Interactions hôte-pathogène (immunologie), Protéines virales (immunologie), Réaction de polymérisation en chaine en temps réel, Souris, Souris de lignée C57BL, Test ELISA, Échappement immunitaire (physiologie).
- MESH :
- enzymologie : Coronaviridae.
- immunologie : Coronaviridae, Endonucleases, Immunité innée, Infections à coronavirus, Interactions hôte-pathogène, Protéines virales.
- physiologie : Échappement immunitaire.
- Animaux, Cytométrie en flux, Humains, Réaction de polymérisation en chaine en temps réel, Souris, Souris de lignée C57BL, Test ELISA.
English descriptors
- KwdEn :
- Animals, Coronaviridae (enzymology), Coronaviridae (immunology), Coronavirus Infections (immunology), Endonucleases (immunology), Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Host-Pathogen Interactions (immunology), Humans, Immune Evasion (physiology), Immunity, Innate (immunology), Mice, Mice, Inbred C57BL, Real-Time Polymerase Chain Reaction, Viral Proteins (immunology).
- MESH :
- chemical , immunology : Endonucleases, Viral Proteins.
- enzymology : Coronaviridae.
- immunology : Coronaviridae, Coronavirus Infections, Host-Pathogen Interactions, Immunity, Innate.
- physiology : Immune Evasion.
- Animals, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Mice, Mice, Inbred C57BL, Real-Time Polymerase Chain Reaction.
Abstract
Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis-within the replicase complex-suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.
DOI: 10.1371/journal.ppat.1006195
PubMed: 28158275
Affiliations:
- Allemagne, Pays-Bas, Singapour, Suisse, États-Unis
- Basse-Saxe, Canton de Berne, Missouri (État), Ohio, Pennsylvanie, Utrecht (province)
- Berne, Hanovre, Saint-Louis (Missouri), Utrecht
- Université d'Utrecht, Université de Berne, École de médecine (Université Washington de Saint-Louis)
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Le document en format XML
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Diseases and Pathobiology, University of Bern, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName><orgName type="university">Université de Berne</orgName></affiliation></author><author><name sortKey="Stalder, Hanspeter" sort="Stalder, Hanspeter" uniqKey="Stalder H" first="Hanspeter" last="Stalder">Hanspeter Stalder</name><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Infectious Diseases and Pathobiology, University of Bern, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName><orgName type="university">Université de Berne</orgName></affiliation></author><author><name sortKey="Marti, Sabrina" sort="Marti, Sabrina" uniqKey="Marti S" first="Sabrina" last="Marti">Sabrina Marti</name><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Infectious Diseases and Pathobiology, University of Bern, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName><orgName type="university">Université de Berne</orgName></affiliation></author><author><name sortKey="Habjan, Matthias" sort="Habjan, Matthias" uniqKey="Habjan M" first="Matthias" last="Habjan">Matthias Habjan</name><affiliation wicri:level="1"><nlm:affiliation>Max-Planck-Institute of Biochemistry, Martinsried, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Max-Planck-Institute of Biochemistry, Martinsried</wicri:regionArea><wicri:noRegion>Martinsried</wicri:noRegion><wicri:noRegion>Martinsried</wicri:noRegion><wicri:noRegion>Martinsried</wicri:noRegion></affiliation></author><author><name sortKey="Cervantes Barragan, Luisa" sort="Cervantes Barragan, Luisa" uniqKey="Cervantes Barragan L" first="Luisa" last="Cervantes-Barragan">Luisa Cervantes-Barragan</name><affiliation wicri:level="4"><nlm:affiliation>Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Elliot, Ruth" sort="Elliot, Ruth" uniqKey="Elliot R" first="Ruth" last="Elliot">Ruth Elliot</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Karl, Nadja" sort="Karl, Nadja" uniqKey="Karl N" first="Nadja" last="Karl">Nadja Karl</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Medical Virology, Justus-Liebig-University, Giessen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Medical Virology, Justus-Liebig-University, Giessen</wicri:regionArea><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion></affiliation></author><author><name sortKey="Gaughan, Christina" sort="Gaughan, Christina" uniqKey="Gaughan C" first="Christina" last="Gaughan">Christina Gaughan</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Van Kuppeveld, Frank J M" sort="Van Kuppeveld, Frank J M" uniqKey="Van Kuppeveld F" first="Frank J M" last="Van Kuppeveld">Frank J M. 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Silverman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Keller, Markus" sort="Keller, Markus" uniqKey="Keller M" first="Markus" last="Keller">Markus Keller</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald-Insel Riems</wicri:regionArea><wicri:noRegion>Greifswald-Insel Riems</wicri:noRegion><wicri:noRegion>Greifswald-Insel Riems</wicri:noRegion><wicri:noRegion>Greifswald-Insel Riems</wicri:noRegion></affiliation></author><author><name sortKey="Ludewig, Burkhard" sort="Ludewig, Burkhard" uniqKey="Ludewig B" first="Burkhard" last="Ludewig">Burkhard Ludewig</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Immunobiology, Kantonsspital St.Gallen, St.Gallen</wicri:regionArea><wicri:noRegion>St.Gallen</wicri:noRegion></affiliation></author><author><name sortKey="Bergmann, Cornelia C" sort="Bergmann, Cornelia C" uniqKey="Bergmann C" first="Cornelia C" last="Bergmann">Cornelia C. Bergmann</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Medical Virology, Justus-Liebig-University, Giessen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Medical Virology, Justus-Liebig-University, Giessen</wicri:regionArea><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion></affiliation></author><author><name sortKey="Weiss, Susan R" sort="Weiss, Susan R" uniqKey="Weiss S" first="Susan R" last="Weiss">Susan R. Weiss</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Kalinke, Ulrich" sort="Kalinke, Ulrich" uniqKey="Kalinke U" first="Ulrich" last="Kalinke">Ulrich Kalinke</name><affiliation wicri:level="3"><nlm:affiliation>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Hanovre</settlement></placeName></affiliation></author><author><name sortKey="Thiel, Volker" sort="Thiel, Volker" uniqKey="Thiel V" first="Volker" last="Thiel">Volker Thiel</name><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Infectious Diseases and Pathobiology, University of Bern, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName><orgName type="university">Université de Berne</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28158275</idno><idno type="pmid">28158275</idno><idno type="doi">10.1371/journal.ppat.1006195</idno><idno type="wicri:Area/PubMed/Corpus">000B57</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000B57</idno><idno type="wicri:Area/PubMed/Curation">000B57</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000B57</idno><idno type="wicri:Area/PubMed/Checkpoint">000B32</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000B32</idno><idno type="wicri:Area/Ncbi/Merge">002D62</idno><idno type="wicri:Area/Ncbi/Curation">002D62</idno><idno type="wicri:Area/Ncbi/Checkpoint">002D62</idno><idno type="wicri:Area/Main/Merge">000E49</idno><idno type="wicri:Area/Main/Curation">000E47</idno><idno type="wicri:Area/Main/Exploration">000E47</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication.</title><author><name sortKey="Kindler, Eveline" sort="Kindler, Eveline" uniqKey="Kindler E" first="Eveline" last="Kindler">Eveline Kindler</name><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Infectious Diseases and Pathobiology, University of Bern, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName><orgName type="university">Université de Berne</orgName></affiliation></author><author><name sortKey="Gil Cruz, Cristina" sort="Gil Cruz, Cristina" uniqKey="Gil Cruz C" first="Cristina" last="Gil-Cruz">Cristina Gil-Cruz</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Immunobiology, Kantonsspital St.Gallen, St.Gallen</wicri:regionArea><wicri:noRegion>St.Gallen</wicri:noRegion></affiliation></author><author><name sortKey="Spanier, Julia" sort="Spanier, Julia" uniqKey="Spanier J" first="Julia" last="Spanier">Julia Spanier</name><affiliation wicri:level="3"><nlm:affiliation>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Hanovre</settlement></placeName></affiliation></author><author><name sortKey="Li, Yize" sort="Li, Yize" uniqKey="Li Y" first="Yize" last="Li">Yize Li</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Wilhelm, Jochen" sort="Wilhelm, Jochen" uniqKey="Wilhelm J" first="Jochen" last="Wilhelm">Jochen Wilhelm</name><affiliation wicri:level="1"><nlm:affiliation>Universities Giessen & Marburg Lung Center (UGMLC), Deutsches Zentrum für Lungenforschung (DZL), Giessen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Universities Giessen & Marburg Lung Center (UGMLC), Deutsches Zentrum für Lungenforschung (DZL), Giessen</wicri:regionArea><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion></affiliation></author><author><name sortKey="Rabouw, Huib H" sort="Rabouw, Huib H" uniqKey="Rabouw H" first="Huib H" last="Rabouw">Huib H. Rabouw</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Zust, Roland" sort="Zust, Roland" uniqKey="Zust R" first="Roland" last="Züst">Roland Züst</name><affiliation wicri:level="1"><nlm:affiliation>Singapore Immunology Network, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Singapore Immunology Network</wicri:regionArea></affiliation></author><author><name sortKey="Hwang, Mihyun" sort="Hwang, Mihyun" uniqKey="Hwang M" first="Mihyun" last="Hwang">Mihyun Hwang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="V Kovski, Philip" sort="V Kovski, Philip" uniqKey="V Kovski P" first="Philip" last="V'Kovski">Philip V'Kovski</name><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Infectious Diseases and Pathobiology, University of Bern, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName><orgName type="university">Université de Berne</orgName></affiliation></author><author><name sortKey="Stalder, Hanspeter" sort="Stalder, Hanspeter" uniqKey="Stalder H" first="Hanspeter" last="Stalder">Hanspeter Stalder</name><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Infectious Diseases and Pathobiology, University of Bern, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName><orgName type="university">Université de Berne</orgName></affiliation></author><author><name sortKey="Marti, Sabrina" sort="Marti, Sabrina" uniqKey="Marti S" first="Sabrina" last="Marti">Sabrina Marti</name><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Infectious Diseases and Pathobiology, University of Bern, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName><orgName type="university">Université de Berne</orgName></affiliation></author><author><name sortKey="Habjan, Matthias" sort="Habjan, Matthias" uniqKey="Habjan M" first="Matthias" last="Habjan">Matthias Habjan</name><affiliation wicri:level="1"><nlm:affiliation>Max-Planck-Institute of Biochemistry, Martinsried, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Max-Planck-Institute of Biochemistry, Martinsried</wicri:regionArea><wicri:noRegion>Martinsried</wicri:noRegion><wicri:noRegion>Martinsried</wicri:noRegion><wicri:noRegion>Martinsried</wicri:noRegion></affiliation></author><author><name sortKey="Cervantes Barragan, Luisa" sort="Cervantes Barragan, Luisa" uniqKey="Cervantes Barragan L" first="Luisa" last="Cervantes-Barragan">Luisa Cervantes-Barragan</name><affiliation wicri:level="4"><nlm:affiliation>Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Elliot, Ruth" sort="Elliot, Ruth" uniqKey="Elliot R" first="Ruth" last="Elliot">Ruth Elliot</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Karl, Nadja" sort="Karl, Nadja" uniqKey="Karl N" first="Nadja" last="Karl">Nadja Karl</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Medical Virology, Justus-Liebig-University, Giessen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Medical Virology, Justus-Liebig-University, Giessen</wicri:regionArea><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion></affiliation></author><author><name sortKey="Gaughan, Christina" sort="Gaughan, Christina" uniqKey="Gaughan C" first="Christina" last="Gaughan">Christina Gaughan</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Van Kuppeveld, Frank J M" sort="Van Kuppeveld, Frank J M" uniqKey="Van Kuppeveld F" first="Frank J M" last="Van Kuppeveld">Frank J M. Van Kuppeveld</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Silverman, Robert H" sort="Silverman, Robert H" uniqKey="Silverman R" first="Robert H" last="Silverman">Robert H. Silverman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Keller, Markus" sort="Keller, Markus" uniqKey="Keller M" first="Markus" last="Keller">Markus Keller</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald-Insel Riems</wicri:regionArea><wicri:noRegion>Greifswald-Insel Riems</wicri:noRegion><wicri:noRegion>Greifswald-Insel Riems</wicri:noRegion><wicri:noRegion>Greifswald-Insel Riems</wicri:noRegion></affiliation></author><author><name sortKey="Ludewig, Burkhard" sort="Ludewig, Burkhard" uniqKey="Ludewig B" first="Burkhard" last="Ludewig">Burkhard Ludewig</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Immunobiology, Kantonsspital St.Gallen, St.Gallen</wicri:regionArea><wicri:noRegion>St.Gallen</wicri:noRegion></affiliation></author><author><name sortKey="Bergmann, Cornelia C" sort="Bergmann, Cornelia C" uniqKey="Bergmann C" first="Cornelia C" last="Bergmann">Cornelia C. Bergmann</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Medical Virology, Justus-Liebig-University, Giessen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Medical Virology, Justus-Liebig-University, Giessen</wicri:regionArea><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion></affiliation></author><author><name sortKey="Weiss, Susan R" sort="Weiss, Susan R" uniqKey="Weiss S" first="Susan R" last="Weiss">Susan R. Weiss</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Kalinke, Ulrich" sort="Kalinke, Ulrich" uniqKey="Kalinke U" first="Ulrich" last="Kalinke">Ulrich Kalinke</name><affiliation wicri:level="3"><nlm:affiliation>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Hanovre</settlement></placeName></affiliation></author><author><name sortKey="Thiel, Volker" sort="Thiel, Volker" uniqKey="Thiel V" first="Volker" last="Thiel">Volker Thiel</name><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Infectious Diseases and Pathobiology, University of Bern, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName><orgName type="university">Université de Berne</orgName></affiliation></author></analytic><series><title level="j">PLoS pathogens</title><idno type="eISSN">1553-7374</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Coronaviridae (enzymology)</term><term>Coronaviridae (immunology)</term><term>Coronavirus Infections (immunology)</term><term>Endonucleases (immunology)</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Flow Cytometry</term><term>Host-Pathogen Interactions (immunology)</term><term>Humans</term><term>Immune Evasion (physiology)</term><term>Immunity, Innate (immunology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Real-Time Polymerase Chain Reaction</term><term>Viral Proteins (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Coronaviridae (enzymologie)</term><term>Coronaviridae (immunologie)</term><term>Cytométrie en flux</term><term>Endonucleases (immunologie)</term><term>Humains</term><term>Immunité innée (immunologie)</term><term>Infections à coronavirus (immunologie)</term><term>Interactions hôte-pathogène (immunologie)</term><term>Protéines virales (immunologie)</term><term>Réaction de polymérisation en chaine en temps réel</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Test ELISA</term><term>Échappement immunitaire (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Endonucleases</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Coronaviridae</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Coronaviridae</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Coronaviridae</term><term>Endonucleases</term><term>Immunité innée</term><term>Infections à coronavirus</term><term>Interactions hôte-pathogène</term><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronaviridae</term><term>Coronavirus Infections</term><term>Host-Pathogen Interactions</term><term>Immunity, Innate</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Échappement immunitaire</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Immune Evasion</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Flow Cytometry</term><term>Humans</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Real-Time Polymerase Chain Reaction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cytométrie en flux</term><term>Humains</term><term>Réaction de polymérisation en chaine en temps réel</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Test ELISA</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis-within the replicase complex-suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Pays-Bas</li><li>Singapour</li><li>Suisse</li><li>États-Unis</li></country><region><li>Basse-Saxe</li><li>Canton de Berne</li><li>Missouri (État)</li><li>Ohio</li><li>Pennsylvanie</li><li>Utrecht (province)</li></region><settlement><li>Berne</li><li>Hanovre</li><li>Saint-Louis (Missouri)</li><li>Utrecht</li></settlement><orgName><li>Université d'Utrecht</li><li>Université de Berne</li><li>École de médecine (Université Washington de Saint-Louis)</li></orgName></list><tree><country name="Suisse"><region name="Canton de Berne"><name sortKey="Kindler, Eveline" sort="Kindler, Eveline" uniqKey="Kindler E" first="Eveline" last="Kindler">Eveline Kindler</name></region><name sortKey="Gil Cruz, Cristina" sort="Gil Cruz, Cristina" uniqKey="Gil Cruz C" first="Cristina" last="Gil-Cruz">Cristina Gil-Cruz</name><name sortKey="Ludewig, Burkhard" sort="Ludewig, Burkhard" uniqKey="Ludewig B" first="Burkhard" last="Ludewig">Burkhard Ludewig</name><name sortKey="Marti, Sabrina" sort="Marti, Sabrina" uniqKey="Marti S" first="Sabrina" last="Marti">Sabrina Marti</name><name sortKey="Stalder, Hanspeter" sort="Stalder, Hanspeter" uniqKey="Stalder H" first="Hanspeter" last="Stalder">Hanspeter Stalder</name><name sortKey="Thiel, Volker" sort="Thiel, Volker" uniqKey="Thiel V" first="Volker" last="Thiel">Volker Thiel</name><name sortKey="V Kovski, Philip" sort="V Kovski, Philip" uniqKey="V Kovski P" first="Philip" last="V'Kovski">Philip V'Kovski</name></country><country name="Allemagne"><region name="Basse-Saxe"><name sortKey="Spanier, Julia" sort="Spanier, Julia" uniqKey="Spanier J" first="Julia" last="Spanier">Julia Spanier</name></region><name sortKey="Habjan, Matthias" sort="Habjan, Matthias" uniqKey="Habjan M" first="Matthias" last="Habjan">Matthias Habjan</name><name sortKey="Kalinke, Ulrich" sort="Kalinke, Ulrich" uniqKey="Kalinke U" first="Ulrich" last="Kalinke">Ulrich Kalinke</name><name sortKey="Karl, Nadja" sort="Karl, Nadja" uniqKey="Karl N" first="Nadja" last="Karl">Nadja Karl</name><name sortKey="Keller, Markus" sort="Keller, Markus" uniqKey="Keller M" first="Markus" last="Keller">Markus Keller</name><name sortKey="Wilhelm, Jochen" sort="Wilhelm, Jochen" uniqKey="Wilhelm J" first="Jochen" last="Wilhelm">Jochen Wilhelm</name><name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name></country><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Li, Yize" sort="Li, Yize" uniqKey="Li Y" first="Yize" last="Li">Yize Li</name></region><name sortKey="Bergmann, Cornelia C" sort="Bergmann, Cornelia C" uniqKey="Bergmann C" first="Cornelia C" last="Bergmann">Cornelia C. Bergmann</name><name sortKey="Cervantes Barragan, Luisa" sort="Cervantes Barragan, Luisa" uniqKey="Cervantes Barragan L" first="Luisa" last="Cervantes-Barragan">Luisa Cervantes-Barragan</name><name sortKey="Elliot, Ruth" sort="Elliot, Ruth" uniqKey="Elliot R" first="Ruth" last="Elliot">Ruth Elliot</name><name sortKey="Gaughan, Christina" sort="Gaughan, Christina" uniqKey="Gaughan C" first="Christina" last="Gaughan">Christina Gaughan</name><name sortKey="Hwang, Mihyun" sort="Hwang, Mihyun" uniqKey="Hwang M" first="Mihyun" last="Hwang">Mihyun Hwang</name><name sortKey="Silverman, Robert H" sort="Silverman, Robert H" uniqKey="Silverman R" first="Robert H" last="Silverman">Robert H. Silverman</name><name sortKey="Weiss, Susan R" sort="Weiss, Susan R" uniqKey="Weiss S" first="Susan R" last="Weiss">Susan R. Weiss</name></country><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Rabouw, Huib H" sort="Rabouw, Huib H" uniqKey="Rabouw H" first="Huib H" last="Rabouw">Huib H. Rabouw</name></region><name sortKey="Van Kuppeveld, Frank J M" sort="Van Kuppeveld, Frank J M" uniqKey="Van Kuppeveld F" first="Frank J M" last="Van Kuppeveld">Frank J M. Van Kuppeveld</name></country><country name="Singapour"><noRegion><name sortKey="Zust, Roland" sort="Zust, Roland" uniqKey="Zust R" first="Roland" last="Züst">Roland Züst</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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