Coronavirus papain-like proteases negatively regulate antiviral innate immune response through disruption of STING-mediated signaling.
Identifieur interne : 001D43 ( Main/Exploration ); précédent : 001D42; suivant : 001D44Coronavirus papain-like proteases negatively regulate antiviral innate immune response through disruption of STING-mediated signaling.
Auteurs : Li Sun [République populaire de Chine] ; Yaling Xing ; Xiaojuan Chen ; Yang Zheng ; Yudong Yang ; Daniel B. Nichols ; Mark A. Clementz ; Bridget S. Banach ; Kui Li ; Susan C. Baker ; Zhongbin ChenSource :
- PloS one [ 1932-6203 ] ; 2012.
Descripteurs français
- KwdFr :
- Animaux, Biocatalyse, Cellules HEK293, Cellules Vero, Coronavirus humain NL63 (enzymologie), Coronavirus humain NL63 (physiologie), Cysteine endopeptidases (), Cysteine endopeptidases (métabolisme), Facteur-3 de régulation d'interféron (métabolisme), Humains, I-kappa B Kinase (métabolisme), Immunité innée, Interférons (métabolisme), Membrane cellulaire (enzymologie), Multimérisation de protéines, Protéines adaptatrices de la transduction du signal (métabolisme), Protéines membranaires (), Protéines membranaires (métabolisme), Protéines virales (), Protéines virales (métabolisme), Structure quaternaire des protéines, Structure tertiaire des protéines, Transduction du signal (immunologie), Ubiquitinylation (immunologie), Virus du SRAS (enzymologie), Virus du SRAS (physiologie).
- MESH :
- enzymologie : Coronavirus humain NL63, Membrane cellulaire, Virus du SRAS.
- immunologie : Transduction du signal, Ubiquitinylation.
- métabolisme : Cysteine endopeptidases, Facteur-3 de régulation d'interféron, I-kappa B Kinase, Interférons, Protéines adaptatrices de la transduction du signal, Protéines membranaires, Protéines virales.
- physiologie : Coronavirus humain NL63, Virus du SRAS.
- Animaux, Biocatalyse, Cellules HEK293, Cellules Vero, Cysteine endopeptidases, Humains, Immunité innée, Multimérisation de protéines, Protéines membranaires, Protéines virales, Structure quaternaire des protéines, Structure tertiaire des protéines.
English descriptors
- KwdEn :
- Adaptor Proteins, Signal Transducing (metabolism), Animals, Biocatalysis, Cell Membrane (enzymology), Chlorocebus aethiops, Coronavirus NL63, Human (enzymology), Coronavirus NL63, Human (physiology), Cysteine Endopeptidases (chemistry), Cysteine Endopeptidases (metabolism), HEK293 Cells, Humans, I-kappa B Kinase (metabolism), Immunity, Innate, Interferon Regulatory Factor-3 (metabolism), Interferons (metabolism), Membrane Proteins (chemistry), Membrane Proteins (metabolism), Protein Multimerization, Protein Structure, Quaternary, Protein Structure, Tertiary, SARS Virus (enzymology), SARS Virus (physiology), Signal Transduction (immunology), Ubiquitination (immunology), Vero Cells, Viral Proteins (chemistry), Viral Proteins (metabolism).
- MESH :
- chemical , chemistry : Cysteine Endopeptidases, Membrane Proteins, Viral Proteins.
- chemical , metabolism : Adaptor Proteins, Signal Transducing, Cysteine Endopeptidases, I-kappa B Kinase, Interferon Regulatory Factor-3, Interferons, Membrane Proteins, Viral Proteins.
- enzymology : Cell Membrane, Coronavirus NL63, Human, SARS Virus.
- immunology : Signal Transduction, Ubiquitination.
- physiology : Coronavirus NL63, Human, SARS Virus.
- Animals, Biocatalysis, Chlorocebus aethiops, HEK293 Cells, Humans, Immunity, Innate, Protein Multimerization, Protein Structure, Quaternary, Protein Structure, Tertiary, Vero Cells.
Abstract
Viruses have evolved elaborate mechanisms to evade or inactivate the complex system of sensors and signaling molecules that make up the host innate immune response. Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKε, leading to IRF-3 activation and subsequent induction of interferon (IFN). We found that expression of the membrane anchored PLP domain from human HCoV-NL63 (PLP2-TM) or SARS-CoV (PLpro-TM) inhibits STING-mediated activation of IRF-3 nuclear translocation and induction of IRF-3 dependent promoters. Both catalytically active and inactive forms of CoV PLPs co-immunoprecipitated with STING, and viral replicase proteins co-localize with STING in HCoV-NL63-infected cells. Ectopic expression of catalytically active PLP2-TM blocks STING dimer formation and negatively regulates assembly of STING-MAVS-TBK1/IKKε complexes required for activation of IRF-3. STING dimerization was also substantially reduced in cells infected with SARS-CoV. Furthermore, the level of ubiquitinated forms of STING, RIG-I, TBK1 and IRF-3 are reduced in cells expressing wild type or catalytic mutants of PLP2-TM, likely contributing to disruption of signaling required for IFN induction. These results describe a new mechanism used by CoVs in which CoV PLPs negatively regulate antiviral defenses by disrupting the STING-mediated IFN induction.
DOI: 10.1371/journal.pone.0030802
PubMed: 22312431
Affiliations:
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Le document en format XML
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<term>Cell Membrane (enzymology)</term>
<term>Chlorocebus aethiops</term>
<term>Coronavirus NL63, Human (enzymology)</term>
<term>Coronavirus NL63, Human (physiology)</term>
<term>Cysteine Endopeptidases (chemistry)</term>
<term>Cysteine Endopeptidases (metabolism)</term>
<term>HEK293 Cells</term>
<term>Humans</term>
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<term>Immunity, Innate</term>
<term>Interferon Regulatory Factor-3 (metabolism)</term>
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<term>Membrane Proteins (metabolism)</term>
<term>Protein Multimerization</term>
<term>Protein Structure, Quaternary</term>
<term>Protein Structure, Tertiary</term>
<term>SARS Virus (enzymology)</term>
<term>SARS Virus (physiology)</term>
<term>Signal Transduction (immunology)</term>
<term>Ubiquitination (immunology)</term>
<term>Vero Cells</term>
<term>Viral Proteins (chemistry)</term>
<term>Viral Proteins (metabolism)</term>
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<term>Biocatalyse</term>
<term>Cellules HEK293</term>
<term>Cellules Vero</term>
<term>Coronavirus humain NL63 (enzymologie)</term>
<term>Coronavirus humain NL63 (physiologie)</term>
<term>Cysteine endopeptidases ()</term>
<term>Cysteine endopeptidases (métabolisme)</term>
<term>Facteur-3 de régulation d'interféron (métabolisme)</term>
<term>Humains</term>
<term>I-kappa B Kinase (métabolisme)</term>
<term>Immunité innée</term>
<term>Interférons (métabolisme)</term>
<term>Membrane cellulaire (enzymologie)</term>
<term>Multimérisation de protéines</term>
<term>Protéines adaptatrices de la transduction du signal (métabolisme)</term>
<term>Protéines membranaires ()</term>
<term>Protéines membranaires (métabolisme)</term>
<term>Protéines virales ()</term>
<term>Protéines virales (métabolisme)</term>
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<term>Structure tertiaire des protéines</term>
<term>Transduction du signal (immunologie)</term>
<term>Ubiquitinylation (immunologie)</term>
<term>Virus du SRAS (enzymologie)</term>
<term>Virus du SRAS (physiologie)</term>
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<term>Viral Proteins</term>
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<term>Cysteine Endopeptidases</term>
<term>I-kappa B Kinase</term>
<term>Interferon Regulatory Factor-3</term>
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<term>Viral Proteins</term>
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<term>Humans</term>
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<term>Protein Multimerization</term>
<term>Protein Structure, Quaternary</term>
<term>Protein Structure, Tertiary</term>
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<term>Biocatalyse</term>
<term>Cellules HEK293</term>
<term>Cellules Vero</term>
<term>Cysteine endopeptidases</term>
<term>Humains</term>
<term>Immunité innée</term>
<term>Multimérisation de protéines</term>
<term>Protéines membranaires</term>
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<front><div type="abstract" xml:lang="en">Viruses have evolved elaborate mechanisms to evade or inactivate the complex system of sensors and signaling molecules that make up the host innate immune response. Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKε, leading to IRF-3 activation and subsequent induction of interferon (IFN). We found that expression of the membrane anchored PLP domain from human HCoV-NL63 (PLP2-TM) or SARS-CoV (PLpro-TM) inhibits STING-mediated activation of IRF-3 nuclear translocation and induction of IRF-3 dependent promoters. Both catalytically active and inactive forms of CoV PLPs co-immunoprecipitated with STING, and viral replicase proteins co-localize with STING in HCoV-NL63-infected cells. Ectopic expression of catalytically active PLP2-TM blocks STING dimer formation and negatively regulates assembly of STING-MAVS-TBK1/IKKε complexes required for activation of IRF-3. STING dimerization was also substantially reduced in cells infected with SARS-CoV. Furthermore, the level of ubiquitinated forms of STING, RIG-I, TBK1 and IRF-3 are reduced in cells expressing wild type or catalytic mutants of PLP2-TM, likely contributing to disruption of signaling required for IFN induction. These results describe a new mechanism used by CoVs in which CoV PLPs negatively regulate antiviral defenses by disrupting the STING-mediated IFN induction.</div>
</front>
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<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="Clementz, Mark A" sort="Clementz, Mark A" uniqKey="Clementz M" first="Mark A" last="Clementz">Mark A. Clementz</name>
<name sortKey="Li, Kui" sort="Li, Kui" uniqKey="Li K" first="Kui" last="Li">Kui Li</name>
<name sortKey="Nichols, Daniel B" sort="Nichols, Daniel B" uniqKey="Nichols D" first="Daniel B" last="Nichols">Daniel B. Nichols</name>
<name sortKey="Xing, Yaling" sort="Xing, Yaling" uniqKey="Xing Y" first="Yaling" last="Xing">Yaling Xing</name>
<name sortKey="Yang, Yudong" sort="Yang, Yudong" uniqKey="Yang Y" first="Yudong" last="Yang">Yudong Yang</name>
<name sortKey="Zheng, Yang" sort="Zheng, Yang" uniqKey="Zheng Y" first="Yang" last="Zheng">Yang Zheng</name>
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<country name="République populaire de Chine"><noRegion><name sortKey="Sun, Li" sort="Sun, Li" uniqKey="Sun L" first="Li" last="Sun">Li Sun</name>
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