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

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...

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Published in:Virologica Sinica 2023-02, Vol.38 (1), p.84-95
Main Authors: Huang, Huaguo, Dang, Wen, Shi, Zhengwang, Ding, Mingyang, Xu, Fan, Li, Tao, Feng, Tao, Zheng, Haixue, Xiao, Shuqi
Format: Article
Language:English
Subjects:
African Swine Fever - prevention & control
African swine fever virus (ASFV)
African Swine Fever Virus - genetics
Animals
Antiviral Agents
Differentially expressed genes (DEGs)
Immunity, Innate - genetics
Interferon Type I
MGF505-2R
Multigene families (MGFs)
Swine
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Summary: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. •The MGF505-2R is highly transcribed throughout the ASFV replication cycle.•The ASFV MGF505-2R-deficient mutant ASFV-Δ2R induced a more pronounced innate immune response in vitro.•Pharmacological activation of classic antiviral immune response synergized in inhibition of ASFV replication.
ISSN:1995-820X
1674-0769
1995-820X
DOI:10.1016/j.virs.2022.11.009