African swine fever virus S273R protein antagonizes type I interferon production by interfering with TBK1 and IRF3 interaction

Hui Li; Xiaojie Zheng; You Li; Yingqi Zhu; Yangyang Xu; Zilong Yu; Wen-Hai Feng

doi:10.1016/j.virs.2023.08.009

December 2023

. doi: 10.1016/j.virs.2023.08.009

Citation: Hui Li, Xiaojie Zheng, You Li, Yingqi Zhu, Yangyang Xu, Zilong Yu, Wen-Hai Feng. African swine fever virus S273R protein antagonizes type I interferon production by interfering with TBK1 and IRF3 interaction .VIROLOGICA SINICA, 2023, 38(6) : 911-921. http://dx.doi.org/10.1016/j.virs.2023.08.009

非洲猪瘟病毒S273R蛋白通过干扰TBK1和IRF3相互作用拮抗I型干扰素的产生

李慧 ^a,b,c,d ,
郑小杰 ^a,b,c,d ,
李尤 ^a,b,c,d ,
朱英琦 ^a,b,c,d ,
徐杨洋 ^a,b,c,d ,
于子龙 ^a,b,c,d ,
封文海 ^a,b,c,d,,

中国农业大学

通讯作者： 封文海, whfeng@cau.edu.cn
收稿日期： 2023-03-09
录用日期： 2023-08-28

摘要

非洲猪瘟（ASF）最初在东非被报道为一种急性出血热。非洲猪瘟病毒（African swine fever virus，ASFV）是一种具有二十面体结构的复杂DNA病毒，可编码多种毒力因子来抵抗宿主先天免疫反应。S273R蛋白（pS273R）是SUMO-1特异性半胱氨酸蛋白酶，可通过切割聚合蛋白影响病毒包装。在本研究中，我们发现pS273R是抑制cGAS-STING介导的I型干扰素（IFN-I）产生的重要拮抗病毒因子。详细分析表明，pS273R通过与干扰素调节因子3（IRF3）相互作用抑制IFN-I的产生。随后，我们发现pS273R破坏了TBK1和IRF3之间的相互作用，导致IRF3磷酸化和二聚化受到抑制。缺失和点突变实验证明pS273R不依赖于其半胱氨酸蛋白酶活性抑制IFN-I的产生。这些发现将有助于我们进一步了解ASFV的发病机制。
- 非洲猪瘟病毒
- , cGAS-STING
- , S273R
- , IRF3
- , TBK1
- , I型干扰素(IFN-I)

African swine fever virus S273R protein antagonizes type I interferon production by interfering with TBK1 and IRF3 interaction

Hui Li ^a,b,c,d ,
Xiaojie Zheng ^a,b,c,d ,
You Li ^a,b,c,d ,
Yingqi Zhu ^a,b,c,d ,
Yangyang Xu ^a,b,c,d ,
Zilong Yu ^a,b,c,d ,
Wen-Hai Feng ^a,b,c,d,,

a. State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China;
b. Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China;
c. Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China;
d. Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China

Corresponding author: Wen-Hai Feng, whfeng@cau.edu.cn
Received Date: 09 March 2023
Accepted Date: 28 August 2023

Abstract

African swine fever (ASF) is originally reported in East Africa as an acute hemorrhagic fever. African swine fever virus (ASFV) is a giant and complex DNA virus with icosahedral structure and encodes a variety of virulence factors to resist host innate immune response. S273R protein (pS273R), as a SUMO-1 specific cysteine protease, can affect viral packaging by cutting polymeric proteins. In this study, we found that pS273R was an important antagonistic viral factor that suppressed cGAS-STING-mediated type I interferon (IFN-I) production. A detailed analysis showed that pS273R inhibited IFN-I production by interacting with interferon regulatory factor 3 (IRF3). Subsequently, we showed that pS273R disrupted the association between TBK1 and IRF3, leading to the repressed IRF3 phosphorylation and dimerization. Deletion and point mutation analysis verified that pS273R impaired IFN-I production independent of its cysteine protease activity. These findings will help us further understand ASFV pathogenesis.
- African swine fever virus (ASFV)
- , cGAS-STING
- , S273R
- , IRF3
- , TBK1
- , Type I interferon (IFN-I)

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Electronic Supplementary Material

10.1016j.virs.2023.08.009-ESM.docx