应激颗粒与病毒的相互制约

黄羽,胡斯奇,郭斐

Interaction between stress granules and viruses

Huang Yu,Hu Siqi,Guo Fei

图1 病毒感染诱导SGs形成及诱发先天性免疫反应机制图 病毒感染细胞后,病毒基因组RNA激活PKR,使elF2α磷酸化,抑制翻译的起始,从而抑制了病毒蛋白质的合成,也诱发SGs的形成。SGs的组成成分多样,包含病毒RNA、RNA结合蛋白和翻译起始因子等,尤其还包括许多先天性免疫模式识别分子(MDA5/ RIG-I/LDP2等);这些模式识别分子可结合病毒RNA,进而将信号传递至线粒体外膜上的MAVS,激活TBK1/IKK的磷酸化,从而使转录因子IRF3/7以及NF-κB入核,激活Ⅰ型干扰素和一些炎性因子的表达和分泌;干扰素经自分泌或旁分泌与细胞膜干扰素受体结合后,激活胞内的STAT1/2磷酸化,而后同IRF9一起入核,识别IRSE区域,激活表达多种ISGs,产生抗病毒作用。另外,OAS/RNase L也是SGs的组成成分,可切割病毒RNA,被切割后的病毒RNA也可被模式识别分子识别,进一步活化抗病毒免疫通路。病毒也通过多种方式来拮抗这种抗病毒作用,如ANCV可抑制PKR的二聚化,HCV可通过PP1来去除eIF2α的磷酸化,PV/TMEV/ZIKV等可切割G3BP1,以及多种病毒可通过与SGs的成分结合的方式来拮抗SGs的形成。OAS: 2°,5°-oligoadenlate synthetase; IRSE: interferon stimulated respnonse element; IRF: interferon regulatory factor; RIG-I: retinoic acid inducible gene I; STAT: signal transducer and activator of transcription; IFNR: interferon receptor; IRF: interferon regulatory factor; ISG: interferon-stimulated gene; MDA5: melanoma differentiation-associated protein 5; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; TRIM25: tripartite motif-containing protein 25; TIA1: T cell restricted intracellular antigen-1; TIAR: TIA1-related protein;PABP: poly(A)-binding protein; G3BP1: Ras-GTPase-activating protein SH3-domain-binding protein 1.

Fig. 1 Mechanism of how virus infection induces SG formation and innate immune responses