2. Academic Validation
  3. African swine fever virus pS273R antagonizes stress granule formation by cleaving the nucleating protein G3BP1 to facilitate viral replication

African swine fever virus pS273R antagonizes stress granule formation by cleaving the nucleating protein G3BP1 to facilitate viral replication

  • J Biol Chem. 2023 May 18;104844. doi: 10.1016/j.jbc.2023.104844.
Tingting Li 1,  Xuewen Li 2,  Xiao Wang 1,  Xin Chen 1,  Gaihong Zhao 1,  Chuanxia Liu 1,  Miaofei Bao 1,  Jie Song 1,  Jiangnan Li 1,  Li Huang 1,  Jun Rong 3,  Kegong Tian 4,  Junhua Deng 5,  Jianzhong Zhu 6,  Xuehui Cai 7,  Zhigao Bu 7,  Jun Zheng 8,  Changjiang Weng 9
Affiliations

Affiliations

  • 1 Division of Fundamental Immunology, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China; Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin 150069, China.
  • 2 Division of Fundamental Immunology, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China; Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin 150069, China; College of Life Sciences, Yangtze University, Jingzhou 434025, China.
  • 3 College of Life Sciences, Yangtze University, Jingzhou 434025, China.
  • 4 National Research Center for Veterinary Medicine, Luoyang 471003, China.
  • 5 Luoyang Putai Biotechnology Co., Ltd, Luoyang 471003, China.
  • 6 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
  • 7 Division of Fundamental Immunology, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China.
  • 8 Division of Fundamental Immunology, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China; Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin 150069, China. Electronic address: zhengjun01@caas.cn.
  • 9 Division of Fundamental Immunology, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China; Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin 150069, China. Electronic address: wengchangjiang@caas.cn.
PMID: 37209818 DOI: 10.1016/j.jbc.2023.104844
Abstract

Cytoplasmic stress granules (SGs) are generally triggered by stress-induced translation arrest for storing mRNAs. Recently, it has been shown that SGs are regulated by different stimulators including viral Infection, which is involved in the Antiviral activity of host cells to limit viral propagation. To survive, several viruses have been reported to execute various strategies, such as modulating SGs formation, to create optimal surroundings for viral replication. African swine fever virus (ASFV) is one of the most notorious pathogens in the global pig industry. However, the interplay between ASFV Infection and SGs formation remains largely unknown. In this study, we found that ASFV Infection inhibited SGs formation. Through SGs inhibitory screening, we found that several ASFV-encoded proteins are involved in inhibition of SGs formation. Among them, an ASFV S273R protein (pS273R), the only cysteine Protease encoded by the ASFV genome significantly affected SGs formation. ASFV pS273R interacted with G3BP1, a vital nucleating protein of SGs formation. Furthermore, we found that ASFV pS273R cleaved G3BP1 at the G140-F141 to produce two fragments (G3BP1-N1-140 and G3BP1-C141-456). Interestingly, both of the pS273R-cleaved fragments of G3BP1 lost the ability to induce SGs formation and Antiviral activity. Taken together, our finding reveals that the proteolytic cleavage of G3BP1 by ASFV pS273R is a novel mechanism by which ASFV counteracts host stress and innate Antiviral responses.

Keywords

African Swine Fever Virus; G3BP1; IFN production; Stress granules; Viral replication; pS273R.

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