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

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

  • J Immunol. 2022 Feb 1;208(3):753-761. doi: 10.4049/jimmunol.2100684.
Chao Sui 1,  Tongyang Xiao 2 3,  Shengyuan Zhang 2 3,  Hongxiang Zeng 2 3,  Yi Zheng 1,  Bingyu Liu 1,  Gang Xu 4 3,  Chengjiang Gao 5,  Zheng Zhang 4 3 6 7
Affiliations

Affiliations

  • 1 Key Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China.
  • 2 Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong Province, China.
  • 3 The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province, China.
  • 4 Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong Province, China; [email protected] [email protected] [email protected].
  • 5 Key Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China; [email protected] [email protected] [email protected].
  • 6 Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science, Shenzhen, Guangdong Province, China; and.
  • 7 Guangdong Key laboratory for anti-infection Drug Quality Evaluation, Shenzhen, Guangdong Province, China.
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.

Figures
Products