Negative Regulation of RNF90 on RNA Virus-Triggered Antiviral Immune Responses Targeting MAVS.
Negative Regulation of RNF90 on RNA Virus-Triggered Antiviral Immune Responses Targeting MAVS.
复制标题
RNF90 对 RNA 病毒引发的针对 MAVS 的抗病毒免疫反应的负调控。
DOI：
10.3389/fimmu.2021.730483
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Yang B;Zhang G;Qin X;Huang Y;Ren X;Sun J;Ma S;Liu Y;Song D;Liu Y;Cui Y;Wang H;Wang J
抗病毒先天免疫是宿主抵御病毒感染的第一道防线。线粒体抗病毒信号转导蛋白(MAVS)是RNA病毒诱导的抗病毒信号转导途径中的关键蛋白，又称Medicf/IPS-1/VISA。我们以前的研究表明，E3泛素蛋白连接酶环指蛋白(RNF90)通过靶向降解来负调控细胞的抗病毒反应，尽管它在RNA病毒感染中的作用尚不清楚。这项研究表明，RNF90对RNF90沉默的PMA-THP1细胞、RNF90缺陷细胞(包括HaCaT、MEF和BMDM)和RNF90缺陷小鼠的RNA病毒触发的抗病毒先天免疫反应具有负面调节作用。然而，RNF90调节RNA病毒触发的独立于刺痛的抗病毒先天免疫反应。RNF90促进K48连接的MAV泛素化及其蛋白酶体依赖的降解，导致先天免疫反应的抑制。综上所述，我们的研究结果提示了RNF90在抗病毒天然免疫中的新功能和新机制。
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.