科学研究
20170523 USP13 negatively regulates antiviral responses by deubiquitinating STING.
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Nat Commun.2017 May 23;8:15534. doi: 10.1038/ncomms15534.

USP13 negatively regulates antiviral responses by deubiquitinating STING.

Sun H1,Zhang Q1,Jing YY1,Zhang M1,Wang HY1,Cai Z1,Liuyu T1,Zhang ZD2,Xiong TC2,Wu Y3,Zhu QY4,Yao J1,Shu HB2,Lin D5,Zhong B1,2.

Author information

1 Department of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.

2 Department of Immunology, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China.

3 National Institute of Biological Sciences, Beijing 102206, China.

4 State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.

5 Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Abstract

STING (also known as MITA) is critical for host defence against viruses and the activity of STING is regulated by ubiquitination. However, the deubiquitination of STING is not fully understood. Here, we show that ubiquitin-specific protease 13 (USP13) is a STING-interacting protein that catalyses deubiquitination of STING. Knockdown or knockout of USP13 potentiates activation of IRF3 and NF-κB and expression of downstream genes after HSV-1 infection or transfection of DNA ligands. USP13 deficiency results in impaired replication of HSV-1. Consistently, USP13 deficient mice are more resistant than wild-type littermates to lethal HSV-1 infection. Mechanistically, USP13 deconjugates polyubiquitin chains from STING and prevents the recruitment of TBK1 to the signalling complex, thereby negatively regulating cellular antiviral responses. Our study thus uncovers a function of USP13 in innate antiviral immunity and provides insight into the regulation of innate immunity.

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