Middle east respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response.
Identifieur interne : 001B47 ( Main/Exploration ); précédent : 001B46; suivant : 001B48Middle east respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response.
Auteurs : Kam-Leung Siu [Hong Kong] ; Man Lung Yeung ; Kin-Hang Kok ; Kit-San Yuen ; Chun Kew ; Pak-Yin Lui ; Chi-Ping Chan ; Herman Tse ; Patrick C Y. Woo ; Kwok-Yung Yuen ; Dong-Yan JinSource :
- Journal of virology [ 1098-5514 ] ; 2014.
Descripteurs français
- KwdFr :
- Cartographie d'interactions entre protéines, Coronavirus (immunologie), DEAD-box RNA helicases (antagonistes et inhibiteurs), Humains, Hélicase IFIH1 inductrice de l'interféron, Interactions hôte-pathogène, Interférons (antagonistes et inhibiteurs), Liaison aux protéines, Lignée cellulaire, Protéine-58 à domaine DEAD, Protéines de liaison à l'ARN (métabolisme), Protéines virales (métabolisme), Échappement immunitaire.
- MESH :
- antagonistes et inhibiteurs : DEAD-box RNA helicases, Interférons.
- immunologie : Coronavirus.
- métabolisme : Protéines de liaison à l'ARN, Protéines virales.
- Cartographie d'interactions entre protéines, Humains, Hélicase IFIH1 inductrice de l'interféron, Interactions hôte-pathogène, Liaison aux protéines, Lignée cellulaire, Protéine-58 à domaine DEAD, Échappement immunitaire.
English descriptors
- KwdEn :
- Cell Line, Coronavirus (immunology), DEAD Box Protein 58, DEAD-box RNA Helicases (antagonists & inhibitors), Host-Pathogen Interactions, Humans, Immune Evasion, Interferon-Induced Helicase, IFIH1, Interferons (antagonists & inhibitors), Protein Binding, Protein Interaction Mapping, RNA-Binding Proteins (metabolism), Viral Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : DEAD-box RNA Helicases, Interferons.
- chemical , metabolism : RNA-Binding Proteins, Viral Proteins.
- chemical : DEAD Box Protein 58, Interferon-Induced Helicase, IFIH1.
- immunology : Coronavirus.
- Cell Line, Host-Pathogen Interactions, Humans, Immune Evasion, Protein Binding, Protein Interaction Mapping.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen that causes severe disease in human. MERS-CoV is closely related to bat coronaviruses HKU4 and HKU5. Evasion of the innate antiviral response might contribute significantly to MERS-CoV pathogenesis, but the mechanism is poorly understood. In this study, we characterized MERS-CoV 4a protein as a novel immunosuppressive factor that antagonizes type I interferon production. MERS-CoV 4a protein contains a double-stranded RNA-binding domain capable of interacting with poly(I · C). Expression of MERS-CoV 4a protein suppressed the interferon production induced by poly(I · C) or Sendai virus. RNA binding of MERS-CoV 4a protein was required for IFN antagonism, a property shared by 4a protein of bat coronavirus HKU5 but not by the counterpart in bat coronavirus HKU4. MERS-CoV 4a protein interacted with PACT in an RNA-dependent manner but not with RIG-I or MDA5. It inhibited PACT-induced activation of RIG-I and MDA5 but did not affect the activity of downstream effectors such as RIG-I, MDA5, MAVS, TBK1, and IRF3. Taken together, our findings suggest a new mechanism through which MERS-CoV employs a viral double-stranded RNA-binding protein to circumvent the innate antiviral response by perturbing the function of cellular double-stranded RNA-binding protein PACT. PACT targeting might be a common strategy used by different viruses, including Ebola virus and herpes simplex virus 1, to counteract innate immunity.
DOI: 10.1128/JVI.03649-13
PubMed: 24522921
Affiliations:
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Woo</name></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></author><author><name sortKey="Jin, Dong Yan" sort="Jin, Dong Yan" uniqKey="Jin D" first="Dong-Yan" last="Jin">Dong-Yan Jin</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24522921</idno><idno type="pmid">24522921</idno><idno type="doi">10.1128/JVI.03649-13</idno><idno type="wicri:Area/PubMed/Corpus">001A57</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001A57</idno><idno type="wicri:Area/PubMed/Curation">001A57</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001A57</idno><idno type="wicri:Area/PubMed/Checkpoint">001803</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001803</idno><idno type="wicri:Area/Ncbi/Merge">000C86</idno><idno type="wicri:Area/Ncbi/Curation">000C86</idno><idno type="wicri:Area/Ncbi/Checkpoint">000C86</idno><idno type="wicri:Area/Main/Merge">001B56</idno><idno type="wicri:Area/Main/Curation">001B47</idno><idno type="wicri:Area/Main/Exploration">001B47</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Middle east respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response.</title><author><name sortKey="Siu, Kam Leung" sort="Siu, Kam Leung" uniqKey="Siu K" first="Kam-Leung" last="Siu">Kam-Leung Siu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, University of Hong Kong, Pokfulam, Hong Kong.</nlm:affiliation><country xml:lang="fr">Hong Kong</country><wicri:regionArea>Department of Biochemistry, University of Hong Kong, Pokfulam</wicri:regionArea><wicri:noRegion>Pokfulam</wicri:noRegion></affiliation></author><author><name sortKey="Yeung, Man Lung" sort="Yeung, Man Lung" uniqKey="Yeung M" first="Man Lung" last="Yeung">Man Lung Yeung</name></author><author><name sortKey="Kok, Kin Hang" sort="Kok, Kin Hang" uniqKey="Kok K" first="Kin-Hang" last="Kok">Kin-Hang Kok</name></author><author><name sortKey="Yuen, Kit San" sort="Yuen, Kit San" uniqKey="Yuen K" first="Kit-San" last="Yuen">Kit-San Yuen</name></author><author><name sortKey="Kew, Chun" sort="Kew, Chun" uniqKey="Kew C" first="Chun" last="Kew">Chun Kew</name></author><author><name sortKey="Lui, Pak Yin" sort="Lui, Pak Yin" uniqKey="Lui P" first="Pak-Yin" last="Lui">Pak-Yin Lui</name></author><author><name sortKey="Chan, Chi Ping" sort="Chan, Chi Ping" uniqKey="Chan C" first="Chi-Ping" last="Chan">Chi-Ping Chan</name></author><author><name sortKey="Tse, Herman" sort="Tse, Herman" uniqKey="Tse H" first="Herman" last="Tse">Herman Tse</name></author><author><name sortKey="Woo, Patrick C Y" sort="Woo, Patrick C Y" uniqKey="Woo P" first="Patrick C Y" last="Woo">Patrick C Y. Woo</name></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></author><author><name sortKey="Jin, Dong Yan" sort="Jin, Dong Yan" uniqKey="Jin D" first="Dong-Yan" last="Jin">Dong-Yan Jin</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Line</term><term>Coronavirus (immunology)</term><term>DEAD Box Protein 58</term><term>DEAD-box RNA Helicases (antagonists & inhibitors)</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Immune Evasion</term><term>Interferon-Induced Helicase, IFIH1</term><term>Interferons (antagonists & inhibitors)</term><term>Protein Binding</term><term>Protein Interaction Mapping</term><term>RNA-Binding Proteins (metabolism)</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cartographie d'interactions entre protéines</term><term>Coronavirus (immunologie)</term><term>DEAD-box RNA helicases (antagonistes et inhibiteurs)</term><term>Humains</term><term>Hélicase IFIH1 inductrice de l'interféron</term><term>Interactions hôte-pathogène</term><term>Interférons (antagonistes et inhibiteurs)</term><term>Liaison aux protéines</term><term>Lignée cellulaire</term><term>Protéine-58 à domaine DEAD</term><term>Protéines de liaison à l'ARN (métabolisme)</term><term>Protéines virales (métabolisme)</term><term>Échappement immunitaire</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>DEAD-box RNA Helicases</term><term>Interferons</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>RNA-Binding Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>DEAD Box Protein 58</term><term>Interferon-Induced Helicase, IFIH1</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>DEAD-box RNA helicases</term><term>Interférons</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines de liaison à l'ARN</term><term>Protéines virales</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Immune Evasion</term><term>Protein Binding</term><term>Protein Interaction Mapping</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cartographie d'interactions entre protéines</term><term>Humains</term><term>Hélicase IFIH1 inductrice de l'interféron</term><term>Interactions hôte-pathogène</term><term>Liaison aux protéines</term><term>Lignée cellulaire</term><term>Protéine-58 à domaine DEAD</term><term>Échappement immunitaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen that causes severe disease in human. MERS-CoV is closely related to bat coronaviruses HKU4 and HKU5. Evasion of the innate antiviral response might contribute significantly to MERS-CoV pathogenesis, but the mechanism is poorly understood. In this study, we characterized MERS-CoV 4a protein as a novel immunosuppressive factor that antagonizes type I interferon production. MERS-CoV 4a protein contains a double-stranded RNA-binding domain capable of interacting with poly(I · C). Expression of MERS-CoV 4a protein suppressed the interferon production induced by poly(I · C) or Sendai virus. RNA binding of MERS-CoV 4a protein was required for IFN antagonism, a property shared by 4a protein of bat coronavirus HKU5 but not by the counterpart in bat coronavirus HKU4. MERS-CoV 4a protein interacted with PACT in an RNA-dependent manner but not with RIG-I or MDA5. It inhibited PACT-induced activation of RIG-I and MDA5 but did not affect the activity of downstream effectors such as RIG-I, MDA5, MAVS, TBK1, and IRF3. Taken together, our findings suggest a new mechanism through which MERS-CoV employs a viral double-stranded RNA-binding protein to circumvent the innate antiviral response by perturbing the function of cellular double-stranded RNA-binding protein PACT. PACT targeting might be a common strategy used by different viruses, including Ebola virus and herpes simplex virus 1, to counteract innate immunity.</div></front></TEI><affiliations><list><country><li>Hong Kong</li></country></list><tree><noCountry><name sortKey="Chan, Chi Ping" sort="Chan, Chi Ping" uniqKey="Chan C" first="Chi-Ping" last="Chan">Chi-Ping Chan</name><name sortKey="Jin, Dong Yan" sort="Jin, Dong Yan" uniqKey="Jin D" first="Dong-Yan" last="Jin">Dong-Yan Jin</name><name sortKey="Kew, Chun" sort="Kew, Chun" uniqKey="Kew C" first="Chun" last="Kew">Chun Kew</name><name sortKey="Kok, Kin Hang" sort="Kok, Kin Hang" uniqKey="Kok K" first="Kin-Hang" last="Kok">Kin-Hang Kok</name><name sortKey="Lui, Pak Yin" sort="Lui, Pak Yin" uniqKey="Lui P" first="Pak-Yin" last="Lui">Pak-Yin Lui</name><name sortKey="Tse, Herman" sort="Tse, Herman" uniqKey="Tse H" first="Herman" last="Tse">Herman Tse</name><name sortKey="Woo, Patrick C Y" sort="Woo, Patrick C Y" uniqKey="Woo P" first="Patrick C Y" last="Woo">Patrick C Y. Woo</name><name sortKey="Yeung, Man Lung" sort="Yeung, Man Lung" uniqKey="Yeung M" first="Man Lung" last="Yeung">Man Lung Yeung</name><name sortKey="Yuen, Kit San" sort="Yuen, Kit San" uniqKey="Yuen K" first="Kit-San" last="Yuen">Kit-San Yuen</name><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></noCountry><country name="Hong Kong"><noRegion><name sortKey="Siu, Kam Leung" sort="Siu, Kam Leung" uniqKey="Siu K" first="Kam-Leung" last="Siu">Kam-Leung Siu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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