数字农科院2.0

Induction Of Otud4 By Viral I.nfection Promotes Antiviral Responses T hrough Deubiquitinating And Stabilizing Mavs

文献类型： 外文期刊

作者： Liuyu, TZ; Yu, KY; Ye, LY; Zhang, ZD; Zhang, M; Ren, YJ; Cai, Z; Zhu, QY; Lin, DD; Zhong, B

作者机构：

期刊名称： CELL RESEARCH

ISSN： 1001-0602

年卷期： 2019 年 29 卷 1 期

页码：

收录情况： JCR（2021版） ; CSCD（2020-2021年度） ; 科技核心（2020版）

摘要： The activity and stability of the adapter protein MAVS (also known as VISA, Cardif and IPS-1), which critically mediates cellular antiviral responses, are extensively regulated by ubiquitination. However, the process whereby MAVS is deubiquitinated is unclear. Here, we report that the ovarian tumor family deubiquitinase 4 (OTUD4) targets MAVS for deubiquitination. Viral infection leads to the IRF3/7-dependent upregulation of OTUD4 which interacts with MAVS to remove K48-linked polyubiquitin chains, thereby maintaining MAVS stability and promoting innate antiviral signaling. Knockout or knockdown of OTUD4 impairs RNA virus-triggered activation of IRF3 and NF-kappa B, expression of their downstream target genes, and potentiates VSV replication in vitro and in vivo. Consistently, Cre-ER Otud4(fl/fl) or Lyz2-Cre Otud4(fl/fl) mice produce decreased levels of type I interferons and proinflammatory cytokines and exhibit increased sensitivity to VSV infection compared to their control littermates. In addition, reconstitution of MAVS into OTUD4-deficient cells restores virus-induced expression of downstream genes and cellular antiviral responses. Together, our findings uncover an essential role of OTUD4 in virus-triggered signaling and contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.

分类号：

  • 相关文献
作者其他论文 更多>>