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

  • Corresponding author: Wen-Hai Feng, whfeng@cau.edu.cn
  • Received Date: 09 March 2023
    Accepted Date: 28 August 2023
    Available online: 01 September 2023
  • 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.

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

      Corresponding author: Wen-Hai Feng, whfeng@cau.edu.cn
    • 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

    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.

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