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

Abstract

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

CLC Number:

R392

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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Regulation of viral nucleic acid sensing signaling pathways by ubiquitination modification

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