Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease.
Identifieur interne : 001B14 ( Main/Exploration ); précédent : 001B13; suivant : 001B15Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease.
Auteurs : Xingxing Yang [République populaire de Chine] ; Xiaojuan Chen [République populaire de Chine] ; Guangxing Bian [République populaire de Chine] ; Jian Tu [Australie] ; Yaling Xing [République populaire de Chine] ; Yayun Wang [République populaire de Chine] ; Zhongbin Chen [République populaire de Chine]Source :
- The Journal of general virology [ 1465-2099 ] ; 2014.
Descripteurs français
- KwdFr :
- Alignement de séquences, Coronaviridae (), Coronaviridae (enzymologie), Coronaviridae (génétique), Domaine catalytique, Données de séquences moléculaires, Facteur-3 de régulation d'interféron (métabolisme), Humains, Infections à Coronaviridae (métabolisme), Infections à Coronaviridae (virologie), Interféron bêta (antagonistes et inhibiteurs), Interféron bêta (métabolisme), Maturation post-traductionnelle des protéines, Papaïne (), Papaïne (génétique), Papaïne (métabolisme), Phosphorylation, Polyprotéines (génétique), Polyprotéines (métabolisme), Protéines virales (), Protéines virales (génétique), Protéines virales (métabolisme), Protéolyse, Séquence d'acides aminés, Ubiquitin-specific proteases (), Ubiquitin-specific proteases (génétique), Ubiquitin-specific proteases (métabolisme), Ubiquitine.
- MESH :
- antagonistes et inhibiteurs : Interféron bêta.
- enzymologie : Coronaviridae.
- génétique : Coronaviridae, Papaïne, Polyprotéines, Protéines virales, Ubiquitin-specific proteases.
- métabolisme : Facteur-3 de régulation d'interféron, Infections à Coronaviridae, Interféron bêta, Papaïne, Polyprotéines, Protéines virales, Ubiquitin-specific proteases.
- virologie : Infections à Coronaviridae.
- Alignement de séquences, Coronaviridae, Domaine catalytique, Données de séquences moléculaires, Humains, Maturation post-traductionnelle des protéines, Papaïne, Phosphorylation, Protéines virales, Protéolyse, Séquence d'acides aminés, Ubiquitin-specific proteases, Ubiquitine.
English descriptors
- KwdEn :
- Amino Acid Sequence, Catalytic Domain, Coronaviridae (chemistry), Coronaviridae (enzymology), Coronaviridae (genetics), Coronaviridae Infections (metabolism), Coronaviridae Infections (virology), Humans, Interferon Regulatory Factor-3 (metabolism), Interferon-beta (antagonists & inhibitors), Interferon-beta (metabolism), Molecular Sequence Data, Papain (chemistry), Papain (genetics), Papain (metabolism), Phosphorylation, Polyproteins (genetics), Polyproteins (metabolism), Protein Processing, Post-Translational, Proteolysis, Sequence Alignment, Ubiquitin, Ubiquitin-Specific Proteases (chemistry), Ubiquitin-Specific Proteases (genetics), Ubiquitin-Specific Proteases (metabolism), Viral Proteins (chemistry), Viral Proteins (genetics), Viral Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Interferon-beta.
- chemical , chemistry : Papain, Ubiquitin-Specific Proteases, Viral Proteins.
- chemical , genetics : Papain, Polyproteins, Ubiquitin-Specific Proteases, Viral Proteins.
- chemical , metabolism : Interferon Regulatory Factor-3, Interferon-beta, Papain, Polyproteins, Ubiquitin-Specific Proteases, Viral Proteins.
- chemistry : Coronaviridae.
- enzymology : Coronaviridae.
- genetics : Coronaviridae.
- metabolism : Coronaviridae Infections.
- virology : Coronaviridae Infections.
- Amino Acid Sequence, Catalytic Domain, Humans, Molecular Sequence Data, Phosphorylation, Protein Processing, Post-Translational, Proteolysis, Sequence Alignment, Ubiquitin.
Abstract
The emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe pulmonary disease in humans and represents the second example of a highly pathogenic coronavirus (CoV) following severe acute respiratory syndrome coronavirus (SARS-CoV). Genomic studies revealed that two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), process the polyproteins encoded by the MERS-CoV genomic RNA. We previously reported that SARS-CoV PLpro acts as both deubiquitinase (DUB) and IFN antagonist, but the function of the MERS-CoV PLpro was poorly understood. In this study, we characterized MERS-CoV PLpro, which is a protease and can recognize and process the cleavage sites (CS) of nsp1-2, nsp2-3 and nsp3-4. The LXGG consensus cleavage sites in the N terminus of pp1a/1ab, which is generally essential for CoV PLpro-mediated processing, were also characterized in MERS-CoV. MERS-CoV PLpro, like human SARS-CoV PLpro and NL63-CoV PLP2, is a viral deubiquitinating enzyme. It acts on both K48- and K63-linked ubiquitination and ISG15-linked ISGylation. We confirmed that MERS-CoV PLpro acts as an IFN antagonist through blocking the phosphorylation and nuclear translocation of IFN regulatory factor 3 (IRF3). These findings indicate that MERS-CoV PLpro acts as a viral DUB and suppresses production of IFN-β by an interfering IRF3-mediated signalling pathway, in addition to recognizing and processing the CS at the N terminus of replicase polyprotein to release the non-structural proteins. The characterization of proteolytic processing, DUB and IFN antagonist activities of MERS-CoV PLpro would reveal the interactions between MERS-CoV and its host, and be applicable to develop strategies targeting PLpro for the effective control of MERS-CoV infection.
DOI: 10.1099/vir.0.059014-0
PubMed: 24362959
Affiliations:
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Province 230032</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Xiaojuan" sort="Chen, Xiaojuan" uniqKey="Chen X" first="Xiaojuan" last="Chen">Xiaojuan Chen</name><affiliation wicri:level="1"><nlm:affiliation>Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing 100850</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Bian, Guangxing" sort="Bian, Guangxing" uniqKey="Bian G" first="Guangxing" last="Bian">Guangxing Bian</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Tu, Jian" sort="Tu, Jian" uniqKey="Tu J" first="Jian" last="Tu">Jian Tu</name><affiliation wicri:level="1"><nlm:affiliation>Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109</wicri:regionArea><wicri:noRegion>NSW 2109</wicri:noRegion></affiliation></author><author><name sortKey="Xing, Yaling" sort="Xing, Yaling" uniqKey="Xing Y" first="Yaling" last="Xing">Yaling Xing</name><affiliation wicri:level="1"><nlm:affiliation>Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing 100850</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wang, Yayun" sort="Wang, Yayun" uniqKey="Wang Y" first="Yayun" last="Wang">Yayun Wang</name><affiliation wicri:level="1"><nlm:affiliation>Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Infection and Immunity, Department of 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Sequence</term><term>Catalytic Domain</term><term>Coronaviridae (chemistry)</term><term>Coronaviridae (enzymology)</term><term>Coronaviridae (genetics)</term><term>Coronaviridae Infections (metabolism)</term><term>Coronaviridae Infections (virology)</term><term>Humans</term><term>Interferon Regulatory Factor-3 (metabolism)</term><term>Interferon-beta (antagonists & inhibitors)</term><term>Interferon-beta (metabolism)</term><term>Molecular Sequence Data</term><term>Papain (chemistry)</term><term>Papain (genetics)</term><term>Papain (metabolism)</term><term>Phosphorylation</term><term>Polyproteins (genetics)</term><term>Polyproteins (metabolism)</term><term>Protein Processing, Post-Translational</term><term>Proteolysis</term><term>Sequence Alignment</term><term>Ubiquitin</term><term>Ubiquitin-Specific Proteases (chemistry)</term><term>Ubiquitin-Specific Proteases (genetics)</term><term>Ubiquitin-Specific Proteases (metabolism)</term><term>Viral Proteins (chemistry)</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Alignement de séquences</term><term>Coronaviridae ()</term><term>Coronaviridae (enzymologie)</term><term>Coronaviridae (génétique)</term><term>Domaine catalytique</term><term>Données de séquences moléculaires</term><term>Facteur-3 de régulation d'interféron (métabolisme)</term><term>Humains</term><term>Infections à Coronaviridae (métabolisme)</term><term>Infections à Coronaviridae (virologie)</term><term>Interféron bêta (antagonistes et inhibiteurs)</term><term>Interféron bêta (métabolisme)</term><term>Maturation post-traductionnelle des protéines</term><term>Papaïne ()</term><term>Papaïne (génétique)</term><term>Papaïne (métabolisme)</term><term>Phosphorylation</term><term>Polyprotéines (génétique)</term><term>Polyprotéines (métabolisme)</term><term>Protéines virales ()</term><term>Protéines virales (génétique)</term><term>Protéines virales (métabolisme)</term><term>Protéolyse</term><term>Séquence d'acides aminés</term><term>Ubiquitin-specific proteases ()</term><term>Ubiquitin-specific proteases (génétique)</term><term>Ubiquitin-specific proteases (métabolisme)</term><term>Ubiquitine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Interferon-beta</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Papain</term><term>Ubiquitin-Specific Proteases</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Papain</term><term>Polyproteins</term><term>Ubiquitin-Specific Proteases</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Interferon Regulatory Factor-3</term><term>Interferon-beta</term><term>Papain</term><term>Polyproteins</term><term>Ubiquitin-Specific Proteases</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Interféron bêta</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Coronaviridae</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="genetics" xml:lang="en"><term>Coronaviridae</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronaviridae</term><term>Papaïne</term><term>Polyprotéines</term><term>Protéines virales</term><term>Ubiquitin-specific proteases</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Coronaviridae Infections</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur-3 de régulation d'interféron</term><term>Infections à Coronaviridae</term><term>Interféron bêta</term><term>Papaïne</term><term>Polyprotéines</term><term>Protéines virales</term><term>Ubiquitin-specific proteases</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à Coronaviridae</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronaviridae Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Catalytic Domain</term><term>Humans</term><term>Molecular Sequence Data</term><term>Phosphorylation</term><term>Protein Processing, Post-Translational</term><term>Proteolysis</term><term>Sequence Alignment</term><term>Ubiquitin</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Alignement de séquences</term><term>Coronaviridae</term><term>Domaine catalytique</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Maturation post-traductionnelle des protéines</term><term>Papaïne</term><term>Phosphorylation</term><term>Protéines virales</term><term>Protéolyse</term><term>Séquence d'acides aminés</term><term>Ubiquitin-specific proteases</term><term>Ubiquitine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe pulmonary disease in humans and represents the second example of a highly pathogenic coronavirus (CoV) following severe acute respiratory syndrome coronavirus (SARS-CoV). Genomic studies revealed that two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), process the polyproteins encoded by the MERS-CoV genomic RNA. We previously reported that SARS-CoV PLpro acts as both deubiquitinase (DUB) and IFN antagonist, but the function of the MERS-CoV PLpro was poorly understood. In this study, we characterized MERS-CoV PLpro, which is a protease and can recognize and process the cleavage sites (CS) of nsp1-2, nsp2-3 and nsp3-4. The LXGG consensus cleavage sites in the N terminus of pp1a/1ab, which is generally essential for CoV PLpro-mediated processing, were also characterized in MERS-CoV. MERS-CoV PLpro, like human SARS-CoV PLpro and NL63-CoV PLP2, is a viral deubiquitinating enzyme. It acts on both K48- and K63-linked ubiquitination and ISG15-linked ISGylation. We confirmed that MERS-CoV PLpro acts as an IFN antagonist through blocking the phosphorylation and nuclear translocation of IFN regulatory factor 3 (IRF3). These findings indicate that MERS-CoV PLpro acts as a viral DUB and suppresses production of IFN-β by an interfering IRF3-mediated signalling pathway, in addition to recognizing and processing the CS at the N terminus of replicase polyprotein to release the non-structural proteins. The characterization of proteolytic processing, DUB and IFN antagonist activities of MERS-CoV PLpro would reveal the interactions between MERS-CoV and its host, and be applicable to develop strategies targeting PLpro for the effective control of MERS-CoV infection. </div></front></TEI><affiliations><list><country><li>Australie</li><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Yang, Xingxing" sort="Yang, Xingxing" uniqKey="Yang X" first="Xingxing" last="Yang">Xingxing Yang</name></noRegion><name sortKey="Bian, Guangxing" sort="Bian, Guangxing" uniqKey="Bian G" first="Guangxing" last="Bian">Guangxing Bian</name><name sortKey="Chen, Xiaojuan" sort="Chen, Xiaojuan" uniqKey="Chen X" first="Xiaojuan" last="Chen">Xiaojuan Chen</name><name sortKey="Chen, Zhongbin" sort="Chen, Zhongbin" uniqKey="Chen Z" first="Zhongbin" last="Chen">Zhongbin Chen</name><name sortKey="Wang, Yayun" sort="Wang, Yayun" uniqKey="Wang Y" first="Yayun" last="Wang">Yayun Wang</name><name sortKey="Xing, Yaling" sort="Xing, Yaling" uniqKey="Xing Y" first="Yaling" last="Xing">Yaling Xing</name></country><country name="Australie"><noRegion><name sortKey="Tu, Jian" sort="Tu, Jian" uniqKey="Tu J" first="Jian" last="Tu">Jian Tu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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