2. Academic Validation
  3. Identification of African swine fever virus MGF505-2R as a potent inhibitor of innate immunity in vitro

Identification of African swine fever virus MGF505-2R as a potent inhibitor of innate immunity in vitro

  • Virol Sin. 2023 Feb;38(1):84-95. doi: 10.1016/j.virs.2022.11.009.
Huaguo Huang 1,  Wen Dang 2,  Zhengwang Shi 2,  Mingyang Ding 3,  Fan Xu 2,  Tao Li 2,  Tao Feng 2,  Haixue Zheng 4,  Shuqi Xiao 5
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China.
  • 2 State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
  • 3 State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China; College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China.
  • 4 State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China. Electronic address: [email protected].
  • 5 College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China. Electronic address: [email protected].
PMID: 36442611 DOI: 10.1016/j.virs.2022.11.009
Abstract

African swine fever (ASF) is etiologically an acute, highly contagious and hemorrhagic disease caused by African swine fever virus (ASFV). Due to its genetic variation and phenotypic diversity, until now, no efficient commercial vaccines or therapeutic options are available. The ASFV genome contains a conserved middle region and two flexible ends that code for five multigene families (MGFs), while the biological functions of the MGFs are not fully characterized. Here, ASFV MGF505-2R-deficient mutant ASFV-Δ2R was constructed based on a highly virulent genotype II field isolate ASFV CN/GS/2018 currently circulating in China. Transcriptomic profiling demonstrated that ASFV-Δ2R was capable of inducing a larger number of differentially expressed genes (DEGs) compared with ASFV CN/GS/2018. Hierarchical clustering of up-regulated DEGs revealed that ASFV-Δ2R induced the most dramatic expression of interferon-related genes and inflammatory and innate immune genes, as further validated by RT-qPCR. The GO and KEGG pathway analysis identified significantly enriched pathways involved in pathogen recognition and innate Antiviral immunity. Conversely, pharmacological activation of those Antiviral immune responses by exogenous cytokines, including type I/II IFNs, TNF-α and IL-1β, exerted combinatory effects and synergized in Antiviral capacity against ASFV replication. Collectively, MGF505-2R is a newly identified inhibitor of innate immunity potentially implicated in immune evasion.

Keywords

African swine fever virus (ASFV); Differentially expressed genes (DEGs); MGF505-2R; Multigene families (MGFs).

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