内网质应激反应:调控天然免疫信号传导抵御病毒感染的枢纽

Endoplasmic stress response:A hub regulating innate immunity signaling pathways to resist viral infections

内质网应激(endoplasmic reticulum stress,ERS)是细胞为应对内质网腔内错误折叠与未折叠蛋白聚集以及钙离子平衡紊乱等状况,而激活未折叠蛋白反应(unfolded protein response,UPR)、内质网过载反应和Caspase-12介导的凋亡通路等信号途径的反应过程,是细胞的一种保护性应激行为。ERS主要通过激活细胞内UPR,促进内质网正常功能的恢复。在病毒感染过程中,病毒会“劫持”细胞内质网合成大量病毒蛋白,加之细胞自身蛋白合成的需求,内质网中蛋白质合成超出了细胞的正常处理范围,造成大量未折叠或者错误折叠蛋白的积聚,接着诱导ERS和激活UPR。ERS作为细胞的一种保护性应激反应,在机体抗病毒感染和调节天然免疫反应中发挥着重要的作用。本研究对ERS的产生及功能、ERS与天然免疫信号通路的交互调控以及ERS诱导的细胞凋亡等方面进行了综述,以期为进一步研究抗病毒策略提供新思路。

The endoplasmic reticulum stress(ERS)response is a cellular response of homeostasis upon stimulation with misfolding or unfolded protein and disorder of calcium balance,which results in the unfolded protein response(UPR),endoplasmic reticulum overload response and caspase-12-mediated apoptosis pathway are induced.ERS is mainly induce UPR,which restores the functions of ER.Viruses hijack the cellular translational machinery to produce viral proteins for virus life cycle,leading to the accumulation of unfolded proteins.Subsequently,the ERS response and the activation of UPR can be induced.As a cellular protective response,ERS plays important roles in the antiviral infections and the regulation of innate immune responses.In this review,we summarized the characteristics of ERS production and function,crosstalk with the innate immunity signaling pathways,and its association with apoptosis.This review is expected to facilitate the development of antiviral strategies.