African Swine Fever Virus MGF360-14L Negatively Regulates Type I Interferon Signaling by Targeting IRF3

被引：40

作者：

Wang, Yang ^{[1
]}

Cui, Shuai ^{[1
]}

Xin, Ting ^{[1
]}

Wang, Xixi ^{[2
]}

Yu, Hainan ^{[1
]}

Chen, Shiyu ^{[1
]}

Jiang, Yajun ^{[1
]}

Gao, Xintao ^{[3
]}

Jiang, Yitong ^{[1
]}

Guo, Xiaoyu ^{[1
]}

Jia, Hong ^{[1
]}

Zhu, Hongfei ^{[1
]}

机构：

[1] Chinese Acad Agr Sci, Inst Anim Sci, Beijing, Peoples R China

[2] Chinese Acad Sci, Inst Microbiol, Beijing, Peoples R China

[3] Chinese Acad Agr Sci CAAS, Biotechnol Res Inst, Beijing, Peoples R China

来源：

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY | 2022年 / 11卷

关键词：

African swine fever virus; interferon; IRF3; ubiquitination; immune evasion; UTILITY;

D O I：

10.3389/fcimb.2021.818969

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-beta (IFN-beta) 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.

引用

页数：9

共 42 条

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