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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1382675
This article is part of the Research Topic Animal Viruses: Pathogenesis, Immune Escape, Spatio-Temporal Evolution, Vaccines, and Cross-Species Transmission View all 12 articles

African Swine Fever Virus MGF360-4L Protein Attenuates Type I Interferon Response by Suppressing the Phosphorylation of IRF3

Provisionally accepted
Zhen Wang Zhen Wang 1,2Yuheng He Yuheng He 2Ying Huang Ying Huang 2Wenzhu Zhai Wenzhu Zhai 2Chunhao Tao Chunhao Tao 2Yuanyuan Chu Yuanyuan Chu 2Zhongbao Pang Zhongbao Pang 2Hongfei Zhu Hongfei Zhu 2Peng Zhao Peng Zhao 1*Hong Jia Hong Jia 2*
  • 1 College of Veterinary Medicine, Shandong Agricultural University, Taian, China
  • 2 Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, Beijing, China

The final, formatted version of the article will be published soon.

    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-β 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.

    Keywords: African Swine Fever Virus, MGF360-4L, Type - 1 interferons, suppreess, Phosphorylation

    Received: 06 Feb 2024; Accepted: 26 Aug 2024.

    Copyright: © 2024 Wang, He, Huang, Zhai, Tao, Chu, Pang, Zhu, Zhao and Jia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Peng Zhao, College of Veterinary Medicine, Shandong Agricultural University, Taian, China
    Hong Jia, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, Beijing, China

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