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

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

doi:10.1016/j.virs.2022.11.009

February 2023

. doi: 10.1016/j.virs.2022.11.009

Citation: Huaguo Huang, Wen Dang, Zhengwang Shi, Mingyang Ding, Fan Xu, Tao Li, Tao Feng, Haixue Zheng, Shuqi Xiao. Identification of African swine fever virus MGF505-2R as a potent inhibitor of innate immunity in vitro .VIROLOGICA SINICA, 2023, 38(1) : 84-95. http://dx.doi.org/10.1016/j.virs.2022.11.009

非洲猪瘟病毒MGF505-2R蛋白在细胞水平上具有天然免疫抑制功能

黄华国 ^a ,
党文 ^b ,
石正旺 ^b ,
丁明洋 ^b,c ,
许凡 ^b ,
李涛 ^b ,
冯涛 ^b ,
郑海学 ^b,, ,
肖书奇 ^a,,

a 中国, 陕西, 杨凌, 西北农林科技大学, 兽医学院, 712100;
b 中国, 甘肃, 兰州, 中国农业科学院兰州兽医研究所, 动物病原生物学国家重点实验室, 国家口蹄疫参考实验室, 动物病毒学农业部重点实验室, 730046;
c 中国, 甘肃, 兰州, 甘肃农业大学, 兽医学院, 730070

通讯作者： 郑海学, haixuezheng@163.com; 肖书奇, xiaoshuqi@nwsuaf.edu.cn
收稿日期： 2022-05-05
录用日期： 2022-11-22

摘要

非洲猪瘟（ASF）是由非洲猪瘟病毒（ASFV）引起的一种急性、出血性和高度接触性的传染病。由于ASFV基因组庞大且长度不一致，目前除了越南外在其他国家还没有有效的疫苗或药物阻止ASF的传播。ASFV的基因组由一个中间的保守区和两端的可变区组成，编码至少五个多基因家族（MGF），而MGF的生物学功能还没有完全阐述清楚。为了探索MGF505-2R的机制和调控，本文以目前流行的高致病性的基因II型ASFV CN/GS/2018为模板构建缺失MGF505-2R的ASFV突变毒株ASFV-Δ2R。转录组分析表明，ASFV-Δ2R感染BMDM后与ASFV CN/GS/2018相比可以诱导更多差异表达的DEG。GO富集分析表明ASFV-Δ2R感染细胞后诱导上调的基因大部分与干扰素和炎症以及先天性免疫基因有关，RT-qPCR实验进一步验证了上述结论。KEGG通路分析确定了DEG主要参与的路径与病原体的识别和先天性抗病毒的免疫反应有关。另外在药理学上证明了外源性细胞因子如I/II型IFN，TNF-α和IL-1β等可以协同调控抗病毒的免疫反应，同时抑制ASFV的扩增。总之，MGF505-2R是一个新发现的参与先天性免疫反应的基因，参与宿主的免疫调控和病毒的复制。
- 非洲猪瘟病毒
- , MGF505-2R
- , 先天性免疫反应
- , RNA-Seq

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

Huaguo Huang ^a ,
Wen Dang ^b ,
Zhengwang Shi ^b ,
Mingyang Ding ^b,c ,
Fan Xu ^b ,
Tao Li ^b ,
Tao Feng ^b ,
Haixue Zheng ^b,, ,
Shuqi Xiao ^a,,

a. College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China;
b. 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;
c. College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China

Corresponding author: Haixue Zheng, haixuezheng@163.com Shuqi Xiao, xiaoshuqi@nwsuaf.edu.cn
Received Date: 05 May 2022
Accepted Date: 22 November 2022

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

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