生物
细胞生物学
钻机-I
细胞骨架
肌动蛋白细胞骨架
先天免疫系统
微小病毒
干扰素
肌动蛋白
核糖核酸
病毒学
受体
细胞
基因
遗传学
作者
Dhiraj Acharya,Rebecca Reis,Meta Volcic,Guanqun Liu,May K. Wang,Bing Shao Chia,Rayhane Nchioua,Rüdiger Groß,Jan Münch,Frank Kirchhoff,Konstantin M.J. Sparrer,Michaela U. Gack
出处
期刊:Cell
[Elsevier]
日期:2022-09-01
卷期号:185 (19): 3588-3602.e21
被引量:16
标识
DOI:10.1016/j.cell.2022.08.011
摘要
The current dogma of RNA-mediated innate immunity is that sensing of immunostimulatory RNA ligands is sufficient for the activation of intracellular sensors and induction of interferon (IFN) responses. Here, we report that actin cytoskeleton disturbance primes RIG-I-like receptor (RLR) activation. Actin cytoskeleton rearrangement induced by virus infection or commonly used reagents to intracellularly deliver RNA triggers the relocalization of PPP1R12C, a regulatory subunit of the protein phosphatase-1 (PP1), from filamentous actin to cytoplasmic RLRs. This allows dephosphorylation-mediated RLR priming and, together with the RNA agonist, induces effective RLR downstream signaling. Genetic ablation of PPP1R12C impairs antiviral responses and enhances susceptibility to infection with several RNA viruses including SARS-CoV-2, influenza virus, picornavirus, and vesicular stomatitis virus. Our work identifies actin cytoskeleton disturbance as a priming signal for RLR-mediated innate immunity, which may open avenues for antiviral or adjuvant design.
科研通智能强力驱动
Strongly Powered by AbleSci AI