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

文献类型： 外文期刊

第一作者： Huang, Huaguo

作者： Huang, Huaguo;Xiao, Shuqi;Dang, Wen;Shi, Zhengwang;Ding, Mingyang;Xu, Fan;Li, Tao;Feng, Tao;Zheng, Haixue;Ding, Mingyang

作者机构：

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

期刊名称：VIROLOGICA SINICA （ 影响因子：5.5； 五年影响因子：4.9 ）

ISSN： 1674-0769

年卷期： 2023 年 38 卷 1 期

页码：

收录情况： SCI

摘要： 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-Delta 2R was constructed based on a highly virulent genotype II field isolate ASFV CN/GS/2018 currently circulating in China. Transcriptomic profiling demonstrated that ASFV-Delta 2R 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-Delta 2R 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-alpha and IL-1 beta, 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.

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