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

Sui，Chao1; Xiao，Tongyang2,3; Zhang，Shengyuan2,3; Zeng，Hongxiang2,3; Zheng，Yi1; Liu，Bingyu1; Xu，Gang3,4; Gao，Chengjiang5; Zhang，Zheng3,6,7,8

2022-02-01

10.4049/jimmunol.2100684

JOURNAL OF IMMUNOLOGY   影响因子和分区

0022-1767

1550-6606

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.

SCI

英语

其他

China National Funds for Distinguished Young Scholars[82025022] ; National Natural Science Foundation of China[31730026,81930039] ; Shenzhen Science and Technology Innovation Committee["KQTD20200909113758004","JSGG20200207155251653","JSGG20200225151410198"] ; Central Charity Fund of the Chinese Academy of Medical Sciences[2020-PT310-009] ; Natural Science Foundation of Guangdong Province[2019A1515011072]

Immunology

Immunology

WOS:000752490500004

AMER ASSOC IMMUNOLOGISTS

IMMUNOLOGY

2-s2.0-85123812959

Scopus

1.Key Laboratory of Infection and Immunity of Shandong Province,Department of Immunology,School of Basic Medical Sciences,Shandong University,Jinan,China
2.Institute of Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,Guangdong Province,Shenzhen,China
3.Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Guangdong Province,Shenzhen,China
4.Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong Province, China; zhangzheng1975@aliyun.com cgao@sdu.edu.cn xugang2513@sina.com
5.Key Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China; zhangzheng1975@aliyun.com cgao@sdu.edu.cn xugang2513@sina.com
6.Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong Province, China; cgao@sdu.edu.cn xugang2513@sina.com
7.Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science, Shenzhen, Guangdong Province, China; and
8.Guangdong Key laboratory for anti-infection Drug Quality Evaluation,Guangdong Province,Shenzhen,China

Sui，Chao,Xiao，Tongyang,Zhang，Shengyuan,et al. SARS-CoV-2 NSP13 Inhibits Type I IFN Production by Degradation of TBK1 via p62-Dependent Selective Autophagy[J]. JOURNAL OF IMMUNOLOGY,2022,208(3):753-761.

Sui，Chao.,Xiao，Tongyang.,Zhang，Shengyuan.,Zeng，Hongxiang.,Zheng，Yi.,...&Zhang，Zheng.(2022).SARS-CoV-2 NSP13 Inhibits Type I IFN Production by Degradation of TBK1 via p62-Dependent Selective Autophagy.JOURNAL OF IMMUNOLOGY,208(3),753-761.

Sui，Chao,et al."SARS-CoV-2 NSP13 Inhibits Type I IFN Production by Degradation of TBK1 via p62-Dependent Selective Autophagy".JOURNAL OF IMMUNOLOGY 208.3(2022):753-761.