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

• Published in: Frontiers in immunology 2021-08, Vol.12, p.730483
• Main Authors: Yang, Bo, Zhang, Ge, Qin, Xiao, Huang, Yulu, Ren, Xiaowen, Sun, Jingliang, Ma, Shujun, Liu, Yanzi, Song, Di, Liu, Yue, Cui, Yuhan, Wang, Hui, Wang, Jie
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - immunology; Adaptor Proteins, Signal Transducing - metabolism; Animals; antiviral innate immune responses; Chlorocebus aethiops; Cytokines - genetics; Cytokines - immunology; Cytokines - metabolism; degradation; HaCaT Cells; HEK293 Cells; Host-Pathogen Interactions; Humans; Immunity, Innate; Immunology; MAVS; Mice; Mice, Knockout; Proteasome Endopeptidase Complex - metabolism; Proteolysis; RNF90; Signal Transduction; signaling pathway; THP-1 Cells; Tripartite Motif Proteins - genetics; Tripartite Motif Proteins - immunology; Tripartite Motif Proteins - metabolism; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - immunology; Ubiquitin-Protein Ligases - metabolism; Ubiquitination; Vero Cells; Vesicular Stomatitis - genetics; Vesicular Stomatitis - immunology; Vesicular Stomatitis - metabolism; Vesicular Stomatitis - virology; Vesiculovirus - immunology; Vesiculovirus - pathogenicity
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.730483

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.