Department of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Department of Immunology, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China.
Nat Commun. 2017 May 23;8:15534. doi: 10.1038/ncomms15534.
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.
STING（也称为 MITA）对于宿主防御病毒至关重要，其活性受泛素化调节。然而，STING 的去泛素化作用尚未完全阐明。在这里，我们表明，泛素特异性蛋白酶 13（USP13）是一种与 STING 相互作用的蛋白质，可催化 STING 的去泛素化。USP13 的敲低或敲除增强了 HSV-1 感染或 DNA 配体转染后 IRF3 和 NF-κB 的激活以及下游基因的表达。USP13 缺陷导致 HSV-1 的复制受损。一致地，USP13 缺陷型小鼠比野生型同窝仔对致死性 HSV-1 感染的抵抗力更强。在机制上，USP13 从 STING 上去除多聚泛素链，并阻止 TBK1 招募到信号复合物，从而负调控细胞抗病毒反应。因此，我们的研究揭示了 USP13 在先天抗病毒免疫中的功能，并深入了解了先天免疫的调节。
