泛素化修饰对病毒核酸感知信号通路的调控

doi:10.6040/j.issn.1671-7554.0.2026.1167

摘要/Abstract

摘要： RNA、DNA病毒感染严重威胁机体健康,固有免疫作为宿主抵御病毒入侵的第一道防线,可通过模式识别受体识别病毒病原相关分子模式及损伤相关分子模式,启动下游信号,诱导Ⅰ型干扰素与炎症因子分泌,快速激活抗病毒免疫应答。维甲酸诱导基因I样受体(retinoic acid-inducible gene I-like receptors, RLRs)通路、环鸟苷酸-腺苷酸合成酶-干扰素基因刺激因子通路(cyclic GMP-AMP synthase-stimulator of interferon genes pathway, cGAS-STING)与Toll样受体(Toll-like receptors, TLRs)通路是介导抗病毒固有免疫的三大核心信号通路:RLRs家族的维甲酸诱导基因蛋白I(retinoic acid-inducible gene I protein, RIG-I)、黑色素瘤分化相关基因5(melanoma differentiation-associated gene 5, MDA5)特异性识别胞质RNA病毒,依托线粒体接头蛋白(mitochondrial antiviral signaling protein, MAVS)激活下游信号;cGAS-STING通路则主要感知胞质病毒DNA,通过合成第二信使环磷酸鸟苷-腺苷酸(cyclic GMP-AMP, cGAMP)激活干扰素应答通路;内体定位的TLR3/7/8/9分别识别病毒核酸,通过干扰素TIR结构域衔接蛋白(TIR-domain-containing adaptor-inducing interferon-β, TRIF)或髓样分化原发性反应蛋白88依赖通路启动免疫信号。然而,免疫信号的过度活化会引发炎症因子大量蓄积,造成机体组织与细胞的不可逆损伤,因此免疫稳态的调控对机体抵御病毒感染至关重要。泛素化修饰是调控抗病毒固有免疫的重要翻译后修饰方式之一,通过多种泛素酶和去泛素酶对这些通路的核心受体和关键蛋白进行泛素化修饰,从而精准调控免疫信号。本文综述了泛素化修饰对RLRs、cGAS-STING、TLRs三大经典抗病毒固有免疫通路的调控功能,为抗病毒免疫治疗提供理论依据。

关键词: 泛素化修饰, 抗病毒, 信号通路, 固有免疫, 干扰素

Abstract: RNA and DNA viral infections pose a serious threat to human health. As the hosts first line of defense against viral invasion, the innate immune system recognizes pathogen-associated molecular patterns(PAMPs)and damage-associated molecular patterns(DAMPs)through pattern recognition receptors, thereby initiating downstream signaling pathways that induce the secretion of type I interferons and inflammatory cytokines, rapidly activating the antiviral immune response. RLRs, cGAS-STING, and TLRs constitute three core signaling pathways that mediate antiviral innate immunity. RIG-I and MDA5, members of the RLRs family, specifically recognize cytoplasmic RNA viruses and activate downstream signaling through the MAVS adaptor protein. The cGAS-STING pathway primarily detects cytoplasmic viral DNA and activates the interferon response pathway by synthesizing the second messenger cGAMP. Endosomal-localized TLR3/7/8/9 recognize viral nucleic acids and initiate immune signaling through TRIF- or MyD88-dependent pathways. However, excessive activation of immune signals can lead to a massive accumulation of inflammatory factors, causing irreversible damage to the tissues and cells; therefore, the regulation of immune homeostasis is crucial for the bodys defense against viral infections. Ubiquitination is one of the key post-translational modifications that regulate the innate immune response against viruses. Through the action of various ubiquitin ligases and deubiquitinases, ubiquitination is applied to the core receptors and key proteins in these pathways, thereby precisely regulating immune signaling. This article reviews the regulatory roles of ubiquitination in the three major classical antiviral innate immune pathways-RLRs, cGAS-STING, and TLRs, and provides a theoretical basis for antiviral immunotherapy.

Key words: Ubiquitination, Antiviral, Signal pathway, Innate immunity, Interferon

中图分类号:

R392

宋洋,刘冰玉,高成江. 泛素化修饰对病毒核酸感知信号通路的调控[J]. 山东大学学报 (医学版), 2026, 64(10): 16-25.

SONG Yang, LIU Bingyu, GAO Chengjiang. Regulation of viral nucleic acid sensing signaling pathways by ubiquitination modification[J]. Journal of Shandong University (Health Sciences), 2026, 64(10): 16-25.

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