African swine fever virus MGF360-4L protein attenuates type I interferon response by suppressing the phosphorylation of IRF3

文献类型： 外文期刊

第一作者： Wang, Zhen

作者： Wang, Zhen;Zhao, Peng;Wang, Zhen;He, Yuheng;Huang, Ying;Zhai, Wenzhu;Tao, Chunhao;Chu, Yuanyuan;Pang, Zhongbao;Zhu, Hongfei;Jia, Hong

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关键词： African swine fever virus; MGF360-4L; type I interferon; suppress; phosphorylation

期刊名称：FRONTIERS IN IMMUNOLOGY （ 影响因子：5.9； 五年影响因子：6.8 ）

ISSN： 1664-3224

年卷期： 2024 年 15 卷

页码：

收录情况： SCI

摘要： African swine fever (ASF) is a highly contagious and lethal disease of swine caused by African swine fever virus (ASFV), and the mortality rate caused by virulent stains can approach 100%. Many ASFV viral proteins suppress the interferon production to evade the host's innate immune responses. However, whether ASFV MGF360-4L could inhibit type I interferon (IFN-I) signaling pathway and the underlying molecular mechanisms remain unknown. Our study, indicated that ASFV MGF360-4L could negatively regulates the cGAS-STING mediated IFN-I signaling pathway. Overexpressing ASFV MGF360-4L could inhibit the cGAS/STING signaling pathway by inhibiting the interferon-beta promoter activity, which was induced by cGAS/STING, TBK1, and IRF3-5D, and further reduced the transcriptional levels of ISG15, ISG54, ISG56, STAT1, STAT2, and TYK2. Confocal microscopy and immunoprecipitation revealed that MGF360-4L co-localized and interacted with IRF3, and WB revealed that ASFV MGF360-4L suppressed the phosphorylation of IRF3. 4L-F2 (75-162 aa) and 4L-F3 (146-387 aa) were the crucial immunosuppressive domains and sites. Altogether, our study reveals ASFV MGF360-4L inhibited cGAS-STING mediated IFN-I signaling pathways, which provides insights into an evasion strategy of ASFV involving in host's innate immune responses.

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