2. Academic Validation
  3. African swine fever virus S273R protein antagonizes type I interferon production by interfering with TBK1 and IRF3 interaction

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

  • Virol Sin. 2023 Aug 31;S1995-820X(23)00107-4. doi: 10.1016/j.virs.2023.08.009.
Hui Li 1,  Xiaojie Zheng 1,  You Li 1,  Yingqi Zhu 1,  Yangyang Xu 1,  Zilong Yu 1,  Wen-Hai Feng 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
  • 2 State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China; Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address: [email protected].
PMID: 37659477 DOI: 10.1016/j.virs.2023.08.009
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.

Keywords

African swine fever virus (ASFV); IRF3; S273R; TBK1; Type I interferon (IFN-I); cGAS-STING.

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