2. Academic Validation
  3. African swine fever virus M1249L protein antagonizes type I interferon production via suppressing phosphorylation of TBK1 and degrading IRF3

African swine fever virus M1249L protein antagonizes type I interferon production via suppressing phosphorylation of TBK1 and degrading IRF3

  • Virus Res. 2022 Oct 2:319:198872. doi: 10.1016/j.virusres.2022.198872.
Shuai Cui 1,  Yang Wang 1,  Xintao Gao 2,  Ting Xin 1,  Xixi Wang 3,  Hainan Yu 1,  Shiyu Chen 1,  Yajun Jiang 1,  Qing Chen 4,  Fei Jiang 5,  Dongyue Wang 5,  Xiaoyu Guo 6,  Hong Jia 7,  Hongfei Zhu 8
Affiliations

Affiliations

  • 1 Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.
  • 2 Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.
  • 3 Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • 4 Beijing University of Agriculture, Beijing, China.
  • 5 China Animal Disease Control Center, Beijing, China.
  • 6 Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China. Electronic address: [email protected].
  • 7 Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China. Electronic address: [email protected].
  • 8 Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China. Electronic address: [email protected].
PMID: 35853521 DOI: 10.1016/j.virusres.2022.198872
Abstract

Cyclic GMP-AMP Synthase (cGAS) is a major DNA sensor. The recognition of cytosolic DNA by cGAS triggers a robust innate immune response that restricts the replication of diverse viral pathogens through the type I interferon (IFN) and nuclear factor-κB (NF-κB) pathways. African swine fever virus (ASFV) is a large and complex DNA virus reported to strongly inhibit the cGAS-STING signaling pathway. Herein, 12 ASFV structural proteins were screened to determine their effects on the cGAS-STING pathway. Ectopic expression of the ASFV caspid protein M1249L significantly inhibited the IFN-β promoter activity induced by the cGAS-STING pathway in a dose-dependent manner. And it could also downregulate the levels of IFN-β and several interferon-stimulating genes (ISGs) induced by cGAS-STING and 2'3'-cGAMP. Moreover, ASFV M1249L also suppressed phosphorylation of TBK1 by cGAS and STING overexpression. Further study showed that M1249L co-localized and interacted with interferon regulatory factor 3 (IRF3), which led to induce IRF3 degradation by lysosomal pathway. Taken together, our study revealed a novel strategy utilized by ASFV for cGAS-STING-related immune evasion.

Keywords

African swine fever virus; IRF3; Innate immunity; M1249L; TBK1.

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