非洲猪瘟病毒感染相关调控基因以及毒力基因初步筛选

doi:10.11843/j.issn.0366-6964.2023.07.027

摘要/Abstract

摘要： 本研究旨在初步筛选非洲猪瘟病毒（African swine fever virus，ASFV）感染过程中与宿主相互作用的调控基因以及毒力基因，为非洲猪瘟（African swine fever，ASF）特效药以及疫苗研发提供分子理论基础。利用GSE145954数据集和文献挖掘，分析ASFV强毒株和弱毒株感染后宿主差异表达基因；使用Metascape数据库对差异基因进行基因功能富集分析，通过交互基因检索工具（STRING）数据库建立蛋白相互作用网络，经网络拓扑结构筛选获得病毒感染宿主调控网络关键基因，随后在细胞水平筛选调控该关键基因的ASFV毒力基因。研究发现ECE1、CCL2、CTSB、SCARB2和CD14在ASFV感染单核巨噬细胞和动物全血中均明显上调，HMBS、DYNLL1、UBB、EZH2和SERPINE1则明显下调。蛋白质相互作用（PPI）分析表明，宿主UBB、CCL2、CTSB、EZH2、SERPINE1、CD14和DYNLL1为ASFV感染宿主调控网络关键基因，其中UBB占据核心地位。ASFV B119L、I215L以及MGF360-13L可抑制UBB的表达。结果提示，宿主UBB、CCL2、CTSB、EZH2、SERPINE1、CD14和DYNLL1为病毒感染宿主调控网络关键基因，其中UBB是非洲猪瘟病毒感染的核心基因。B119L、I215L以及MGF360-13L可抑制UBB的表达，为ASFV重要的毒力基因。

关键词: 非洲猪瘟病毒, GEO数据库, 蛋白相互作用, UBB, 毒力分子

Abstract: This study aims to preliminarily screen the regulatory genes and virulence genes that interact with the host during African swine fever virus (ASFV) infection, so as to provide a molecular theoretical basis for the development of specific drugs and vaccines against ASFV. We re-analyzed the differentially expressed genes in the host during high and low virulent ASFV strains infection using GSE145954 and literature mining. The Metascape database was used for gene function enrichment analysis and the protein interaction network was established through the STRING database. The key genes in the regulatory network of viral infection host were obtained through network topology screening, and then the ASFV virulence genes regulating the key genes were screened at the cell level. The study found that ECE1, CCL2, CTSB, SCARB2 and CD14 were significantly up-regulated in ASFV infected mononuclear macrophages and whole blood of animals, while HMBS, DYNLL1, UBB, EZH2 and SERPINE1 were significantly down-regulated. PPI analysis showed that UBB, CCL2, CTBB, EZH2, SERPINE1, CD14 and DYNLL1 in host cells are key genes in the regulatory network of host infected with ASFV, in which UBB played a central role. B119L, I215L and MGF360-13L of ASFV can inhibit the expression of UBB. The results suggest that UBB, CCL2, CTSB, EZH2, SERPINE1, CD14 and DYNLL1 are the key genes in the regulatory network, and UBB is the hub gene during ASFV infection. B119L, I215L and MGF360-13L of ASFV inhibit UBB expression, which are important virulent genes of ASFV.

Key words: African swine fever virus, GEO database, protein interaction, UBB, virulent genes

中图分类号:

S852.659.1

丁晓艳, 何久香, 周晓杨, 周伃欣, 李晋涛. 非洲猪瘟病毒感染相关调控基因以及毒力基因初步筛选[J]. 畜牧兽医学报, 2023, 54(7): 2964-2971.

DING Xiaoyan, HE Jiuxiang, ZHOU Xiaoyang, ZHOU Yuxin, LI Jintao. Preliminary Identification of Host Regulatory Genes and Virulence Genes during African Swine Fever Virus Infection[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(7): 2964-2971.

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