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10.3389/fimmu.2021.662989

http://scihub22266oqcxt.onion/10.3389/fimmu.2021.662989
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34084167!8168463!34084167
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suck abstract from ncbi


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pmid34084167      Front+Immunol 2021 ; 12 (ä): 662989
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  • SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Production Through Ubiquitin-Mediated Degradation of TBK1 #MMPMID34084167
  • Sui L; Zhao Y; Wang W; Wu P; Wang Z; Yu Y; Hou Z; Tan G; Liu Q
  • Front Immunol 2021[]; 12 (ä): 662989 PMID34084167show ga
  • The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of current COVID-19 pandemic, and insufficient production of type I interferon (IFN-I) is associated with the severe forms of the disease. Membrane (M) protein of SARS-CoV-2 has been reported to suppress host IFN-I production, but the underlying mechanism is not completely understood. In this study, SARS-CoV-2 M protein was confirmed to suppress the expression of IFNbeta and interferon-stimulated genes induced by RIG-I, MDA5, IKK?, and TBK1, and to inhibit IRF3 phosphorylation and dimerization caused by TBK1. SARS-CoV-2 M could interact with MDA5, TRAF3, IKK?, and TBK1, and induce TBK1 degradation via K48-linked ubiquitination. The reduced TBK1 further impaired the formation of TRAF3-TANK-TBK1-IKKepsilon complex that leads to inhibition of IFN-I production. Our study revealed a novel mechanism of SARS-CoV-2 M for negative regulation of IFN-I production, which would provide deeper insight into the innate immunosuppression and pathogenicity of SARS-CoV-2.
  • |DEAD Box Protein 58/metabolism[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |I-kappa B Kinase/metabolism[MESH]
  • |Interferon Regulatory Factor-3/metabolism[MESH]
  • |Interferon Type I/*biosynthesis[MESH]
  • |Interferon-Induced Helicase, IFIH1/metabolism[MESH]
  • |Protein Serine-Threonine Kinases/*metabolism[MESH]
  • |Proteolysis[MESH]
  • |Receptors, Immunologic/metabolism[MESH]
  • |SARS-CoV-2/*immunology[MESH]
  • |Signal Transduction[MESH]
  • |TNF Receptor-Associated Factor 3/metabolism[MESH]
  • |Ubiquitin/*metabolism[MESH]


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