Negative Regulation of RNF90 on RNA Virus-Triggered Antiviral Immune Responses Targeting MAVS

Frontiers in Immunology

Di Song¹  Yanzi Liu²  Hui Wang³  Bo Yang³  Jie Wang³  Ge Zhang⁴  Jingliang Sun⁴  Yue Liu⁴  Yuhan Cui⁴  Xiaowen Ren⁴  Xiao Qin⁴  Shujun Ma⁴  Yulu Huang⁴ 

[1] Department of Laboratory Medicine, Fuwai Center China Cardiovascular Hospital, Zhengzhou, China;Department of Laboratory Medicine, the Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China;Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China;Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, China;

关键词: antiviral innate immune responses;    ubiquitination;    degradation;    signaling pathway;    MAVS;    RNF90;   

DOI  :  10.3389/fimmu.2021.730483

来源: DOAJ

【 摘 要 】

The antiviral innate immunity is the first line of host defense against viral infection. Mitochondrial antiviral signaling protein (MAVS, also named Cardif/IPS-1/VISA) is a critical protein in RNA virus-induced antiviral signaling pathways. Our previous research suggested that E3 ubiquitin-protein ligases RING-finger protein (RNF90) negatively regulate cellular antiviral responses by targeting STING for degradation, though its role in RNA virus infection remains unknown. This study demonstrated that RNF90 negatively regulated RNA virus-triggered antiviral innate immune responses in RNF90-silenced PMA-THP1 cells, RNF90-deficient cells (including HaCaTs, MEFs, and BMDMs), and RNF90-deficient mice. However, RNF90 regulated RNA virus-triggered antiviral innate immune responses independent of STING. RNF90 promoted K48-linked ubiquitination of MAVS and its proteasome-dependent degradation, leading to the inhibition of innate immune responses. Altogether, our findings suggested a novel function and mechanism of RNF90 in antiviral innate immunity.

【 授权许可】

Unknown