G3BP1 通过正调控 RIG-I 介导的细胞抗病毒反应来抑制 RNA 病毒复制。

G3BP1 inhibits RNA virus replication by positively regulating RIG-I-mediated cellular antiviral response.

机构信息

State Key Laboratory of Veterinary Etiological Biology and OIE/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China.

出版信息

Cell Death Dis. 2019 Dec 11;10(12):946. doi: 10.1038/s41419-019-2178-9.

Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor and is involved in the innate immune response against RNA viruses infection. Here, we demonstrate that the Ras-GTPase-activating protein SH3-domain-binding protein 1 (G3BP1) serves as a positive regulator of the RIG-I-mediated signaling pathway. G3BP1-deficient cells inhibited RNA virus-triggered induction of downstream antiviral genes. Furthermore, we found that G3BP1 inhibited the replication of Sendai virus and vesicular stomatitis virus, indicating a positive regulation of G3BP1 to cellular antiviral responses. Mechanistically, G3BP1 formed a complex with RNF125 and RIG-I, leading to decreased RNF125 via its auto-ubiquitination; thus, promoting expression of RIG-I. Overall, the results suggest a novel mechanism for G3BP1 in the positive regulation of antiviral signaling mediated by RIG-I.

视黄酸诱导基因 I（RIG-I）是一种模式识别受体，参与针对 RNA 病毒感染的先天免疫反应。在这里，我们证明 Ras-GTPase 激活蛋白 SH3 结构域结合蛋白 1（G3BP1）是 RIG-I 介导的信号通路的正调节剂。G3BP1 缺陷细胞抑制 RNA 病毒触发的下游抗病毒基因的诱导。此外，我们发现 G3BP1 抑制了仙台病毒和水疱性口炎病毒的复制，表明 G3BP1 对细胞抗病毒反应的正调节。在机制上，G3BP1 与 RNF125 和 RIG-I 形成复合物，导致 RNF125 通过自身泛素化减少，从而促进 RIG-I 的表达。总的来说，这些结果表明 G3BP1 在 RIG-I 介导的抗病毒信号的正调控中具有一种新的机制。