tetano
Editor, Senior Moderator
J Immunol
. 2022 Jan 7;ji2100684.
doi: 10.4049/jimmunol.2100684. Online ahead of print.
SARS-CoV-2 NSP13 Inhibits Type I IFN Production by Degradation of TBK1 via p62-Dependent Selective Autophagy
Chao Sui[SUP] 1 [/SUP], Tongyang Xiao[SUP] 2 3 [/SUP], Shengyuan Zhang[SUP] 2 3 [/SUP], Hongxiang Zeng[SUP] 2 3 [/SUP], Yi Zheng[SUP] 1 [/SUP], Bingyu Liu[SUP] 1 [/SUP], Gang Xu[SUP] 4 3 [/SUP], Chengjiang Gao[SUP] 5 [/SUP], Zheng Zhang[SUP] 4 3 6 7 [/SUP]
Affiliations
Abstract
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, and the absence of p62 can also inhibit TBK1 degradation in HEK-293T and HeLa cells. Finally, TBK1 and p62 degradation and p62 aggregation were observed during SARS-CoV-2 infection in HeLa-ACE2 and Calu3 cells. Overall, our study shows that NSP13 inhibits type I IFN production by recruiting TBK1 to p62 for autophagic degradation, enabling it to evade the host innate immune response, which provides new insights into the transmission and pathogenesis of SARS-CoV-2 infection.
. 2022 Jan 7;ji2100684.
doi: 10.4049/jimmunol.2100684. Online ahead of print.
SARS-CoV-2 NSP13 Inhibits Type I IFN Production by Degradation of TBK1 via p62-Dependent Selective Autophagy
Chao Sui[SUP] 1 [/SUP], Tongyang Xiao[SUP] 2 3 [/SUP], Shengyuan Zhang[SUP] 2 3 [/SUP], Hongxiang Zeng[SUP] 2 3 [/SUP], Yi Zheng[SUP] 1 [/SUP], Bingyu Liu[SUP] 1 [/SUP], Gang Xu[SUP] 4 3 [/SUP], Chengjiang Gao[SUP] 5 [/SUP], Zheng Zhang[SUP] 4 3 6 7 [/SUP]
Affiliations
- PMID: 34996837
- DOI: 10.4049/jimmunol.2100684
Abstract
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, and the absence of p62 can also inhibit TBK1 degradation in HEK-293T and HeLa cells. Finally, TBK1 and p62 degradation and p62 aggregation were observed during SARS-CoV-2 infection in HeLa-ACE2 and Calu3 cells. Overall, our study shows that NSP13 inhibits type I IFN production by recruiting TBK1 to p62 for autophagic degradation, enabling it to evade the host innate immune response, which provides new insights into the transmission and pathogenesis of SARS-CoV-2 infection.