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

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

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
Available online: 01 September 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)

Electronic Supplementary Material

10.1016j.virs.2023.08.009-ESM.docx
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