泛素化调控抗病毒天然免疫的研究进展

Regulation of innate antiviral immunity by protein ubiquitination

天然免疫是宿主防御病原微生物入侵的第一道防线,其活化主要通过天然免疫细胞上的模式识别受体(pattern recognition receptors, PRRs)识别病原微生物上相对保守的相关分子模式(pathogen-associated molecular patterns, PAMPs).病毒相关的核酸成分可以被机体Toll样受体(Toll-like receptors, TLRs)、维甲酸诱导基因Ⅰ受体(RIG-I-like receptors, RLRs)以及胞浆DNA受体(cytoplasmic DNA sensors)等识别,通过一系列复杂的细胞信号通路诱导Ⅰ型干扰素(typeⅠinterferon)及炎症因子的表达,从而激发机体抗病毒反应.泛素化修饰是细胞内广泛存在的蛋白质翻译后修饰方式,在宿主防御病原微生物感染的动态调控过程中发挥着重要的作用.已有大量文献报道,天然免疫抗病毒信号通路中的多个关键接头分子可发生泛素化修饰,进而调控机体抗病毒免疫应答反应.本文综述了泛素化修饰在抗病毒天然免疫中的作用及其调控机制.

Innate immunity is the first line of host defense against invading microbes.Activation of innate immunity primarily relies on the recognition of pathogen-associated molecular patterns (PAMPs)by pattern-recognition receptors (PRRs).Viral nucleic acids are recognized by the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)and the Toll-like receptors (TLR)as well as the DNA sensor cyclic GMP-AMP (cGAMP)synthase (cGAS),leading to the production of proinflammatory cytokines and type I interferon and elimination of viral infection.Protein ubiquitination has emerged as a crucial mechanism that regulates signal transduction in diverse biological processes.A variety of key molecules in innate antiviral signaling transduction pathways can be ubiquitinated.The current review summarizes our current knowledge on the functions and regulatory mechanisms of protein ubiquitination in innate antiviral immunity with a focus on the E3 ligases.