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Small‐molecule inhibitors of ubiquitin‐specific protease 7 enhance type‐I interferon antiviral efficacy by destabilizing SOCS1
Author(s) -
Yuan Yukang,
Miao Ying,
Zeng Chenhua,
Liu Jin,
Chen Xiangjie,
Qian Liping,
Wang Xiaofang,
Qian Feng,
Yu Zhengyuan,
Wang Jun,
Qian Guanghui,
Fu Qian,
Lv Haitao,
Zheng Hui
Publication year - 2020
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13147
Subject(s) - stat protein , suppressor of cytokine signaling 1 , interferon , janus kinase , ubiquitin , biology , deubiquitinating enzyme , signal transduction , suppressor of cytokine signalling , cytokine , microbiology and biotechnology , stat , activator (genetics) , socs3 , stat3 , virology , immunology , suppressor , receptor , biochemistry , gene
Summary Type‐I interferons (IFN‐I) are used as common antiviral drugs for a range of viral diseases in clinic. However, the antiviral efficacy of IFN‐I is largely restricted by negative regulators of IFN‐I signaling in cells. Therefore, identification of intracellular inhibitors of IFN‐I signaling is important for developing novel targets to improve IFN‐I antiviral therapy. In this study, we report that the deubiquitinase ubiquitin‐specific protease 7 (USP7) negatively regulates IFN‐I‐mediated antiviral activity. USP7 physically interacts with suppressor of cytokine signaling 1 (SOCS1) and enhances SOCS1 protein stability by deubiquitination effects, which in turn restricts IFN‐I‐induced activation of Janus kinase–signal transducer and activator of transcription 1 signaling. Interestingly, viral infection up‐regulates USP7 and therefore facilitates viral immune evasion. Importantly, the USP7 small‐molecule inhibitors P5091 and P22077 inhibit SOCS1 expression and enhance IFN‐I antiviral efficacy. Our findings identify a novel regulator of IFN‐I antiviral activity and reveal that USP7 inhibitors could be potential enhancement agents for improving IFN‐I antiviral therapy.