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SARS-CoV-2 NSP13 Inhibits Type I IFN Production by Degradation of TBK1 via p62-Dependent Selective Autophagy

J Immunol. 2022-01; 
Chao Sui, Tongyang Xiao, Shengyuan Zhang, Hongxiang Zeng, Yi Zheng, Bingyu Liu, Gang Xu, Chengjiang Gao, Zheng Zhang
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Catalog Antibody  p62 (P0067) was from Sigma-Aldrich, STREP (A00875-40) was from GenScript, and hemagglutinin (HA, HT301-01) Get A Quote

摘要

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has seriously threatened global public health. Severe COVID-19 has been reported to be associated with an impaired IFN response. However, the mechanisms of how SARS-CoV-2 antagonizes the host IFN response are poorly understood. In this study, we report that SARS-CoV-2 helicase NSP13 inhibits type I IFN production by directly targeting TANK-binding kinase 1 (TBK1) for degradation. Interestingly, inhibition of autophagy by genetic knockout of Beclin1 or pharmacological inhibition can rescue NSP13-mediated TBK1 degradation in HEK-293T cells. Subsequent studies revealed that NSP13 recruits TBK1 to p62, an... More

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