非洲猪瘟病毒I226R蛋白抑制cGAS-STING通路介导的天然免疫应答

doi:10.13345/j.cjb.230106

科微学术

生物工程学报

首页 > 过刊浏览>2023年第39卷第12期 >4796-4808. DOI:10.13345/j.cjb.230106

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非洲猪瘟病毒I226R蛋白抑制cGAS-STING通路介导的天然免疫应答
DOI:
                        10.13345/j.cjb.230106
                    
CSTR:
                        32114.14.j.cjb.230106
                    
作者:
                        李亚波李亚波
广西大学动物科学技术学院, 广西 南宁 530000;中国科学院微生物研究所 病原微生物与免疫学重点实验室, 北京 100101
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娄慧聪娄慧聪
广西大学动物科学技术学院, 广西 南宁 530000;中国科学院微生物研究所 病原微生物与免疫学重点实验室, 北京 100101
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赵雨娜赵雨娜
广西大学动物科学技术学院, 广西 南宁 530000;中国科学院微生物研究所 病原微生物与免疫学重点实验室, 北京 100101
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范文辉范文辉
中国科学院微生物研究所 病原微生物与免疫学重点实验室, 北京 100101
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焦鹏涛焦鹏涛
中国科学院微生物研究所 病原微生物与免疫学重点实验室, 北京 100101
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孙蕾孙蕾
中国科学院微生物研究所 病原微生物与免疫学重点实验室, 北京 100101;中国科学院大学, 北京 100049
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罗廷荣罗廷荣
广西大学动物科学技术学院, 广西 南宁 530000
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刘文军刘文军
广西大学动物科学技术学院, 广西 南宁 530000;中国科学院微生物研究所 病原微生物与免疫学重点实验室, 北京 100101;中国科学院大学, 北京 100049
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基金项目:国家重点研发计划(2021YFD1801202)；国家自然科学基金(31941015)；内蒙古自治区科技计划项目(2021ZD0010-04)

The I226R protein of African swine fever virus inhibits the cGAS-STING-mediated innate immune response

Author:

LI Yabo
LI Yabo
Animal Science and Technology College, Guangxi University, Nanning 530000, Guangxi, China;Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
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LOU Huicong
LOU Huicong
Animal Science and Technology College, Guangxi University, Nanning 530000, Guangxi, China;Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
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ZHAO Yuna
ZHAO Yuna
Animal Science and Technology College, Guangxi University, Nanning 530000, Guangxi, China;Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
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FAN Wenhui
FAN Wenhui
Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
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JIAO Pengtao
JIAO Pengtao
Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
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SUN Lei
SUN Lei
Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;University of Chinese Academy of Sciences, Beijing 100049, China
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LUO Tingrong
LUO Tingrong
Animal Science and Technology College, Guangxi University, Nanning 530000, Guangxi, China
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LIU Wenjun
LIU Wenjun
Animal Science and Technology College, Guangxi University, Nanning 530000, Guangxi, China;Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;University of Chinese Academy of Sciences, Beijing 100049, China
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参考文献 [30]

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摘要:

本研究旨在探究非洲猪瘟病毒(African swine fever virus, ASFV) I226R蛋白(I226R protein, pI226R)抑制cGAS-STING信号通路的作用机制。利用双荧光素酶报告系统和实时荧光定量PCR (real-time quantitative PCR, qPCR)证明pI226R显著抑制cGAS-STING通路介导的I型干扰素及干扰素刺激相关基因的产生。免疫共沉淀及激光共聚焦显微镜试验发现pI226R与cGAS蛋白相互作用。免疫印迹分析证明pI226R通过自噬-溶酶体途径促进cGAS蛋白的降解。同时，pI226R阻碍了cGAS与E3泛素连接酶三基序蛋白56 (tripartite motif protein 56, TRIM56)的结合，导致cGAS的单泛素化减弱，从而抑制了cGAS的活化和cGAS-STING通路的激活。总之，本研究证明ASFV pI226R通过拮抗cGAS进而抑制宿主的抗病毒天然免疫反应，进一步增加了对研究ASFV免疫逃逸机制的理解，为疫苗的研发提供了理论基础。

关键词:非洲猪瘟病毒;I226R蛋白;cGAS-STING信号通路;天然免疫应答

Abstract:

This study aimed to explore the mechanism of how African swine fever virus (ASFV) I226R protein inhibits the cGAS-STING signaling pathway. We observed that I226R protein (pI226R) significantly inhibited the cGAS-STING-mediated type I interferons and the interferon-stimulated genes production by dual-luciferase reporter assay system and real-time quantitative PCR. The results of co-immunoprecipitation assay and confocal microscopy showed that pI226R interacted with cGAS. Furthermore, pI226R promoted cGAS degradation through autophagy-lysosome pathway. Moreover, we found that pI226R decreased the binding of cGAS to E3 ligase tripartite motif protein 56 (TRIM56), resulting in the weakened monoubiquitination of cGAS, thus inhibiting the activation of cGAS and cGAS-STING signaling. In conclusion, ASFV pI226R suppresses the antiviral innate immune response by antagonizing cGAS, which contributes to an in-depth understanding of the immune escape mechanism of ASFV and provides a theoretical basis for the development of vaccines.

Key words:African swine fever virus;I226R protein;cGAS-STING signaling pathway;innate immune response

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