美国克利夫兰诊所Michaela U. Gack、德国乌尔姆大学医学中心Konstantin M.J. Sparrer等研究人员合作发现，肌动蛋白细胞骨架重塑为RIG-I类受体的激活提供动力。2022年9月15日出版的《细胞》杂志发表了这项成果。

研究人员发现，肌动蛋白细胞骨架的紊乱为RIG-I样受体（RLR）的激活提供了动力。由病毒感染或常用试剂诱导的肌动蛋白细胞骨架重排，触发了PPP1R12C（蛋白磷酸酶-1（PP1）的一个调节亚基）从丝状肌动蛋白到细胞质RLR的重新定位。这使得去磷酸化介导的RLR启动，并与RNA激动剂一起，诱导有效的RLR下游信号。PPP1R12C的基因敲减会损害抗病毒反应，并增强对几种RNA病毒感染的易感性，包括SARS-CoV-2、流感病毒、小核糖核酸病毒和水泡性口炎病毒。这项工作确定了肌动蛋白细胞骨架紊乱是RLR介导先天免疫的启动信号，这可能为抗病毒或佐剂设计开辟了途径。

据悉，目前RNA介导的先天免疫的教条是，对免疫刺激RNA配体的感应足以激活细胞内传感器和诱导干扰素（IFN）反应。

附：英文原文

Title: Actin cytoskeleton remodeling primes RIG-I-like receptor activation

Author: Dhiraj Acharya, Rebecca Reis, Meta Volcic, GuanQun Liu, May K. Wang, Bing Shao Chia, Rayhane Nchioua, Rüdiger Gro, Jan Münch, Frank Kirchhoff, Konstantin M.J. Sparrer, Michaela U. Gack

Issue&Volume: 2022/09/15

Abstract: The current dogma of RNA-mediated innate immunity is that sensing of immunostimulatoryRNA ligands is sufficient for the activation of intracellular sensors and inductionof interferon (IFN) responses. Here, we report that actin cytoskeleton disturbanceprimes RIG-I-like receptor (RLR) activation. Actin cytoskeleton rearrangement inducedby virus infection or commonly used reagents to intracellularly deliver RNA triggersthe relocalization of PPP1R12C, a regulatory subunit of the protein phosphatase-1(PP1), from filamentous actin to cytoplasmic RLRs. This allows dephosphorylation-mediatedRLR 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 severalRNA viruses including SARS-CoV-2, influenza virus, picornavirus, and vesicular stomatitisvirus. Our work identifies actin cytoskeleton disturbance as a priming signal forRLR-mediated innate immunity, which may open avenues for antiviral or adjuvant design.

DOI: 10.1016/j.cell.2022.08.011

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01060-1