The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection
Identifieur interne : 000F32 ( Main/Exploration ); précédent : 000F31; suivant : 000F33The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection
Auteurs : Anthony R. Fehr [États-Unis] ; Rudragouda Channappanavar [États-Unis] ; Gytis Jankevicius [Royaume-Uni] ; Craig Fett [États-Unis] ; Jincun Zhao [États-Unis, République populaire de Chine] ; Jeremiah Athmer [États-Unis] ; David K. Meyerholz [États-Unis] ; Ivan Ahel [Royaume-Uni] ; Stanley Perlman [États-Unis]Source :
- mBio [ 2150-7511 ] ; 2016.
Descripteurs français
- KwdFr :
- ADP (métabolisme), Animaux, Bronches (cytologie), Bronches (immunologie), Bronches (virologie), Cellules épithéliales (immunologie), Cellules épithéliales (virologie), Charge virale, Co-infection (immunologie), Co-infection (virologie), Coronavirus (), Coronavirus (génétique), Coronavirus (immunologie), Coronavirus (pathogénicité), Cytokines (immunologie), Domaines protéiques, Humains, Immunité innée, Interactions hôte-pathogène, Lignée cellulaire, Mutation, Protéines virales non structurales (), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), Souris, Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (virologie), Virulence, Virus du SRAS (pathogénicité).
- MESH :
- cytologie : Bronches.
- génétique : Coronavirus, Protéines virales non structurales.
- immunologie : Bronches, Cellules épithéliales, Co-infection, Coronavirus, Cytokines, Syndrome respiratoire aigu sévère.
- métabolisme : ADP, Protéines virales non structurales.
- pathogénicité : Coronavirus, Virus du SRAS.
- virologie : Bronches, Cellules épithéliales, Co-infection, Syndrome respiratoire aigu sévère.
- Animaux, Charge virale, Coronavirus, Domaines protéiques, Humains, Immunité innée, Interactions hôte-pathogène, Lignée cellulaire, Mutation, Protéines virales non structurales, Souris, Virulence.
English descriptors
- KwdEn :
- Adenosine Diphosphate (metabolism), Animals, Bronchi (cytology), Bronchi (immunology), Bronchi (virology), Cell Line, Coinfection (immunology), Coinfection (virology), Coronavirus (chemistry), Coronavirus (genetics), Coronavirus (immunology), Coronavirus (pathogenicity), Cytokines (immunology), Epithelial Cells (immunology), Epithelial Cells (virology), Host-Pathogen Interactions, Humans, Immunity, Innate, Mice, Mutation, Protein Domains, SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (virology), Viral Load, Viral Nonstructural Proteins (chemistry), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism), Virulence.
- MESH :
- chemical , chemistry : Viral Nonstructural Proteins.
- chemical , genetics : Viral Nonstructural Proteins.
- chemical , immunology : Cytokines.
- chemical , metabolism : Adenosine Diphosphate, Viral Nonstructural Proteins.
- chemistry : Coronavirus.
- cytology : Bronchi.
- genetics : Coronavirus.
- immunology : Bronchi, Coinfection, Coronavirus, Epithelial Cells, Severe Acute Respiratory Syndrome.
- pathogenicity : Coronavirus, SARS Virus.
- virology : Bronchi, Coinfection, Epithelial Cells, Severe Acute Respiratory Syndrome.
- Animals, Cell Line, Host-Pathogen Interactions, Humans, Immunity, Innate, Mice, Mutation, Protein Domains, Viral Load, Virulence.
Abstract
ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the
Url:
DOI: 10.1128/mBio.01721-16
PubMed: 27965448
PubMed Central: 5156301
Affiliations:
- Royaume-Uni, République populaire de Chine, États-Unis
- Angleterre, Iowa, Oxfordshire
- Iowa City, Oxford
- Université d'Oxford, Université de l'Iowa
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Le document en format XML
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Fehr</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Channappanavar, Rudragouda" sort="Channappanavar, Rudragouda" uniqKey="Channappanavar R" first="Rudragouda" last="Channappanavar">Rudragouda Channappanavar</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Jankevicius, Gytis" sort="Jankevicius, Gytis" uniqKey="Jankevicius G" first="Gytis" last="Jankevicius">Gytis Jankevicius</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Sir William Dunn School of Pathology, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Fett, Craig" sort="Fett, Craig" uniqKey="Fett C" first="Craig" last="Fett">Craig Fett</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Yuexiu District, Guangzhou, Guangdong, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Yuexiu District, Guangzhou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Athmer, Jeremiah" sort="Athmer, Jeremiah" uniqKey="Athmer J" first="Jeremiah" last="Athmer">Jeremiah Athmer</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K." last="Meyerholz">David K. Meyerholz</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Pathology, University of Iowa, Iowa City, Iowa, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Ahel, Ivan" sort="Ahel, Ivan" uniqKey="Ahel I" first="Ivan" last="Ahel">Ivan Ahel</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Sir William Dunn School of Pathology, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author></analytic><series><title level="j">mBio</title><idno type="eISSN">2150-7511</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine Diphosphate (metabolism)</term><term>Animals</term><term>Bronchi (cytology)</term><term>Bronchi (immunology)</term><term>Bronchi (virology)</term><term>Cell Line</term><term>Coinfection (immunology)</term><term>Coinfection (virology)</term><term>Coronavirus (chemistry)</term><term>Coronavirus (genetics)</term><term>Coronavirus (immunology)</term><term>Coronavirus (pathogenicity)</term><term>Cytokines (immunology)</term><term>Epithelial Cells (immunology)</term><term>Epithelial Cells (virology)</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Immunity, Innate</term><term>Mice</term><term>Mutation</term><term>Protein Domains</term><term>SARS Virus (pathogenicity)</term><term>Severe Acute Respiratory Syndrome (immunology)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Viral Load</term><term>Viral Nonstructural Proteins (chemistry)</term><term>Viral Nonstructural Proteins (genetics)</term><term>Viral Nonstructural Proteins (metabolism)</term><term>Virulence</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADP (métabolisme)</term><term>Animaux</term><term>Bronches (cytologie)</term><term>Bronches (immunologie)</term><term>Bronches (virologie)</term><term>Cellules épithéliales (immunologie)</term><term>Cellules épithéliales (virologie)</term><term>Charge virale</term><term>Co-infection (immunologie)</term><term>Co-infection (virologie)</term><term>Coronavirus ()</term><term>Coronavirus (génétique)</term><term>Coronavirus (immunologie)</term><term>Coronavirus (pathogénicité)</term><term>Cytokines (immunologie)</term><term>Domaines protéiques</term><term>Humains</term><term>Immunité innée</term><term>Interactions hôte-pathogène</term><term>Lignée cellulaire</term><term>Mutation</term><term>Protéines virales non structurales ()</term><term>Protéines virales non structurales (génétique)</term><term>Protéines virales non structurales (métabolisme)</term><term>Souris</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Virulence</term><term>Virus du SRAS (pathogénicité)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Cytokines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adenosine Diphosphate</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Bronches</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Bronchi</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus</term><term>Protéines virales non structurales</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Bronches</term><term>Cellules épithéliales</term><term>Co-infection</term><term>Coronavirus</term><term>Cytokines</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Bronchi</term><term>Coinfection</term><term>Coronavirus</term><term>Epithelial Cells</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ADP</term><term>Protéines virales non structurales</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Coronavirus</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Bronches</term><term>Cellules épithéliales</term><term>Co-infection</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Bronchi</term><term>Coinfection</term><term>Epithelial Cells</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Immunity, Innate</term><term>Mice</term><term>Mutation</term><term>Protein Domains</term><term>Viral Load</term><term>Virulence</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Charge virale</term><term>Coronavirus</term><term>Domaines protéiques</term><term>Humains</term><term>Immunité innée</term><term>Interactions hôte-pathogène</term><term>Lignée cellulaire</term><term>Mutation</term><term>Protéines virales non structurales</term><term>Souris</term><term>Virulence</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><p>ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the <italic>Coronavirinae</italic>, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity <italic>in vitro</italic>. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kuny, Cv" uniqKey="Kuny C">CV Kuny</name></author><author><name sortKey="Sullivan, Cs" uniqKey="Sullivan C">CS Sullivan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Atasheva, S" uniqKey="Atasheva S">S Atasheva</name></author><author><name sortKey="Akhrymuk, M" uniqKey="Akhrymuk M">M Akhrymuk</name></author><author><name sortKey="Frolova, Ei" uniqKey="Frolova E">EI Frolova</name></author><author><name sortKey="Frolov, I" uniqKey="Frolov I">I Frolov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goodier, Jl" uniqKey="Goodier J">JL Goodier</name></author><author><name sortKey="Pereira, Gc" 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Egloff</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Royaume-Uni</li><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Iowa</li><li>Oxfordshire</li></region><settlement><li>Iowa City</li><li>Oxford</li></settlement><orgName><li>Université d'Oxford</li><li>Université de l'Iowa</li></orgName></list><tree><country name="États-Unis"><region name="Iowa"><name sortKey="Fehr, Anthony R" sort="Fehr, Anthony R" uniqKey="Fehr A" first="Anthony R." last="Fehr">Anthony R. Fehr</name></region><name sortKey="Athmer, Jeremiah" sort="Athmer, Jeremiah" uniqKey="Athmer J" first="Jeremiah" last="Athmer">Jeremiah Athmer</name><name sortKey="Channappanavar, Rudragouda" sort="Channappanavar, Rudragouda" uniqKey="Channappanavar R" first="Rudragouda" last="Channappanavar">Rudragouda Channappanavar</name><name sortKey="Fett, Craig" sort="Fett, Craig" uniqKey="Fett C" first="Craig" last="Fett">Craig Fett</name><name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K." last="Meyerholz">David K. Meyerholz</name><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Jankevicius, Gytis" sort="Jankevicius, Gytis" uniqKey="Jankevicius G" first="Gytis" last="Jankevicius">Gytis Jankevicius</name></region><name sortKey="Ahel, Ivan" sort="Ahel, Ivan" uniqKey="Ahel I" first="Ivan" last="Ahel">Ivan Ahel</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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