Seneca Valley Virus 3C protease negatively regulates the type I interferon pathway by acting as a viral deubiquitinase

文献类型： 外文期刊

第一作者： Xue, Qiao

作者： Xue, Qiao;Liu, Huisheng;Zhu, Zixiang;Yang, Fan;Liu, Xiangtao;Zheng, Haixue;Xue, Qinghong;Cai, Xuepeng

作者机构：

关键词： Deubiquitinase; Innate immunity; Seneca valley virus; Ubiquitin; 3C-like protease

期刊名称：ANTIVIRAL RESEARCH （ 影响因子：5.97； 五年影响因子：5.801 ）

ISSN： 0166-3542

年卷期： 2018 年 160 卷

页码：

收录情况： SCI

摘要： The mechanisms that enable Seneca Valley Virus (SVV) to escape the host innate immune response are not well known. Previous studies demonstrated that SW 305(pro) suppresses innate immune responses by cleavage of host proteins and degradation of IRF3 and IRF7 protein expression. Here, we showed that SVV 3C protease (3CP(pro)) has deubiquitinating activity. Overexpressed 3CP(pro) inhibits the ubiquitination of cellular substrates, acting on both lysine-48-and lysine-63-linked polyubiquitin chains. SVV infection also possessed deubiquitinating activity. The ubiquitin-proteasome system was significantly involved in SVV replication. Furthermore, 3CP(pro) inhibited the ubiquitination of retinoic acid-inducible gene I (RIG-I), TANK-binding kinase 1 (TBK1), and TNF receptor-associated factor 3 (TRAF3), thereby blocking the expression of interferon (IFN)-beta and IFN stimulated gene 54 (ISG54) mRNAs. A detailed analysis revealed that mutations (H48A, C160A, or H48A/C160A) that ablate the Cys and His residues of 3CP(pro) abrogated its deubiquitinating activity and the ability of 3CP(pro) to block IFN-beta induction. Together, our results demonstrate a novel mechanism developed by SVV 3C(pro) to promote viral replication, and may also provide a novel strategy for improving ubiquitination-based therapy.

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