Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, China.
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
Front Immunol. 2021 Aug 27;12:730483. doi: 10.3389/fimmu.2021.730483. eCollection 2021.
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.
抗病毒先天免疫是宿主防御病毒感染的第一道防线。线粒体抗病毒信号蛋白（MAVS，也称为 Cardif/IPS-1/VISA）是 RNA 病毒诱导的抗病毒信号通路中的关键蛋白。我们之前的研究表明，E3 泛素蛋白连接酶环指蛋白（RNF90）通过靶向 STING 进行降解来负调控细胞抗病毒反应，但其在 RNA 病毒感染中的作用尚不清楚。本研究表明，RNF90 负调控沉默 RNF90 的 PMA-THP1 细胞、RNF90 缺陷细胞（包括 HaCaTs、MEFs 和 BMDMs）和 RNF90 缺陷小鼠中 RNA 病毒触发的抗病毒先天免疫反应。然而，RNF90 调节 RNA 病毒触发的抗病毒先天免疫反应独立于 STING。RNF90 促进 MAVS 的 K48 连接泛素化及其蛋白酶体依赖性降解，从而抑制先天免疫反应。总之，我们的研究结果表明了 RNF90 在抗病毒先天免疫中的新功能和机制。
