非洲猪瘟病毒拮抗宿主cGAS-STING信号通路的研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2023-0681

摘要/Abstract

摘要：

非洲猪瘟病毒（African swine fever virus，ASFV）拥有多种逃逸宿主免疫应答的策略，造成病毒难以被宿主清除。cGAS-STING信号通路介导的天然免疫在抗ASFV感染中发挥了重要作用，然而病毒编码的多个蛋白靶向该通路中的不同分子以拮抗宿主的I型干扰素应答。利用基因编辑技术敲除这些病毒基因后，ASFV对宿主的致病性降低，成为基因缺失疫苗的研制潜在靶点。本文对目前已知参与调控宿主cGAS-STING信号通路的病毒蛋白进行总结，旨在阐明这些蛋白免疫逃逸cGAS-STING信号通路的分子机制，加深对ASFV免疫逃逸策略的理解，以期为ASFV致病机制研究与疫苗创制提供参考。

关键词: 非洲猪瘟病毒, 天然免疫, cGAS-STING信号通路, 免疫逃逸

Abstract:

African swine fever virus（ASFV）possesses multiple strategies for escaping host immune responses, making it difficult for the virus to be cleared by the host. The cGAS-STING pathway, which mediates host innate immune response, is critical for fighting ASFV infection. Nevertheless, numerous viral proteins targeting different molecules involving in the cGAS-STING pathway inhibit type I interferon production. The deletion of partial of these ASFV genes using genome editing technology attenuated the virulence of the virus, which provides targets for the development of gene deletion vaccine. In this review, we summarized current knowledge on the viral proteins of ASFV modulating host cGAS-STING signaling pathway and elucidate the mechanism of these proteins escaping cGAS-STING signaling pathway, which may deepen the understanding of ASFV immune evasion strategy and provide theoretical basis for the research of ASFV pathogenic mechanism and vaccine development.

Key words: African swine fever virus, innate immunity, cGAS-STING signaling pathway, immune escape

赵鸿远, 刘强, 成温玉. 非洲猪瘟病毒拮抗宿主cGAS-STING信号通路的研究进展[J]. 生物技术通报, 2024, 40(3): 109-117.

ZHAO Hong-yuan, LIU Qiang, CHENG Wen-yu. Research Progress in cGAS-STING Signaling Pathway in ASFV Antagonizing Host[J]. Biotechnology Bulletin, 2024, 40(3): 109-117.

图/表 1

图1 cGAS-STING信号通路示意图 AP-1：激活蛋白1；cGAS：环鸟苷酸-腺苷酸合成酶；cGAMP：环鸟苷酸腺苷酸；ER：内质网；IKK：核因子κB抑制剂激酶；IL：白介素；IRF：干扰素调节因子；ISG：干扰素刺激基因；STING：干扰素刺激基因；p-STING：磷酸化的干扰素刺激基因；TBK1：TANK结合激酶

Fig. 1 Schematic diagram of cGAS-STING signal pathway AP-1: Activating protein 1. cGAS: Cyclic GMP-AMP synthase. cGAMP: Cyclic guanosine monophosphate-adenosine monophosphate. ER: Endoplasmic reticulum. IKK: Inhibitor of nuclear factor-κB kinase. IL: Interleukin. IRF: IFN-regulatory factor. ISG: Interferon stimulated gene. STING: Stimulator of interferon gene. p-STING: Phosphorylated STING. TBK1: TANK-binding kinase 1

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