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

被引：46

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

[1] ICTV Virus Taxonomy Profile: Asfarviridae [J].

Alonso, Covadonga ;

Borca, Manuel ;

Dixon, Linda ;

Revilla, Yolanda ;

Rodriguez, Fernando ;

Escribano, Jose M. .

JOURNAL OF GENERAL VIROLOGY, 2018, 99 (05) :613-614

[2] Development of a fluorescent ASFV strain that retains the ability to cause disease in swine [J].

Borca, Manuel V. ;

O'Donnell, Vivian ;

Holinka, Lauren G. ;

Sanford, Brent ;

Azzinaro, Paul A. ;

Risatti, Guillermo R. ;

Gladue, Douglas P. .

SCIENTIFIC REPORTS, 2017, 7

[3] The cGAS-cGAMP-STING Pathway of Cytosolic DNA Sensing and Signaling [J].

Cai, Xin ;

Chiu, Yu-Hsin ;

Chen, Zhijian J. .

MOLECULAR CELL, 2014, 54 (02) :289-296

[4] Identification and utility of innate immune system evasion mechanisms of ASFV [J].

Correia, Silvia ;

Ventura, Sonia ;

Parkhouse, Robert Michael .

VIRUS RESEARCH, 2013, 173 (01) :87-100

[5] INNATE IMMUNITY Pathogen and xenobiotic sensing - back to basics [J].

Cunha, Andreia .

NATURE REVIEWS IMMUNOLOGY, 2012, 12 (06) :400-401

[6] Dengue Virus NS Proteins Inhibit RIG-I/MAVS Signaling by Blocking TBK1/IRF3 Phosphorylation: Dengue Virus Serotype 1 NS4A Is a Unique Interferon-Regulating Virulence Determinant [J].

Dalrymple, Nadine A. ;

Cimica, Velasco ;

Mackow, Erich R. .

MBIO, 2015, 6 (03) :1-12

[7] African swine fever [J].

Dixon, L. K. ;

Sun, H. ;

Roberts, H. .

ANTIVIRAL RESEARCH, 2019, 165 :34-41

[8] Swine TRIM21 restricts FMDV infection via an intracellular neutralization mechanism [J].

Fan, Wenchun ;

Zhang, Dong ;

Qian, Ping ;

Qian, Suhong ;

Wu, Mengge ;

Chen, Huanchun ;

Li, Xiangmin .

ANTIVIRAL RESEARCH, 2016, 127 :32-40

[9] Toll-like Receptors and the Control of Immunity [J].

Fitzgerald, Katherine A. ;

Kagan, Jonathan C. .

CELL, 2020, 180 (06) :1044-1066

[10] DDX56 cooperates with FMDV 3A to enhance FMDV replication by inhibiting the phosphorylation of IRF3 [J].

Fu, Shao-zu ;

Yang, Wen-ping ;

Ru, Yi ;

Zhang, Ke-shan ;

Wang, Yong ;

Liu, Xiang-tao ;

Li, Dan ;

Zheng, Hai-xue .

CELLULAR SIGNALLING, 2019, 64

← 1 2 3 4 5 →