AUTHOR=Wang Yang , Cui Shuai , Xin Ting , Wang Xixi , Yu Hainan , Chen Shiyu , Jiang Yajun , Gao Xintao , Jiang Yitong , Guo Xiaoyu , Jia Hong , Zhu Hongfei TITLE=African Swine Fever Virus MGF360-14L Negatively Regulates Type I Interferon Signaling by Targeting IRF3 JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=11 YEAR=2022 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.818969 DOI=10.3389/fcimb.2021.818969 ISSN=2235-2988 ABSTRACT=

African swine fever (ASF) is a devastating infectious disease caused by African swine fever virus (ASFV). The ASFV genome encodes multiple structural and non-structural proteins that contribute to evasion of host immunity. In this study, we determined that the viral non-structural protein MGF360-14L inhibits interferon-β (IFN-β) promoter activity induced by cGAS-STING signaling. MGF360-14L was also found to downregulate expression of the IRF3 protein and promote its degradation through ubiquitin-meditated proteolysis. Moreover, MGF360-14L was shown to interact with and destabilize IRF3 by facilitating E3 ligase TRIM21-mediated K63-linked ubiquitination of IRF3. Overall, our study revealed that MGF360-14L promotes degradation of IRF3 through TRIM21, thereby inhibiting type I interferon production. These findings provide new insights into the mechanisms underlying ASFV immune evasion.