中国兽医科学2025，Vol.55Issue(12)：1563-1573,11.DOI:10.16656/j.issn.1673-4696.2025.0232
非洲猪瘟病毒pD205R对JAK-STAT信号通路激活的调控作用
African swine fever virus pD205R antagonizes the activation of JAK-STAT signaling pathway
摘要
Abstract
This study investigated the role of the African swine fever virus(ASFV)D205R protein(pD205R)in modulating the JAK-STAT signaling pathway to inform the future development of novel ASF vaccines and therapeutics.To characterize its fundamental biological properties,sequence alignment and subcellular localization analysis of pD205R were performed.Subsequently,we generated stable pD205R-expressing cell lines and employed reporter gene assays,RT-qPCR,and Western-blot to assess the protein's impact on IFN-β-induced JAK-STAT pathway activation.Co-immunoprecipitation and confocal microscopy experiments then revealed an interaction between pD205R and IFNAR1.Finally,truncated pD205R mutants were constructed to map its functional domains.The results showed that pD205R is a highly conserved late-expressed ASFV protein and primarily localizes to the cytoplasm.It specifically inhibited IFN-β-induced STAT1/2 promoter activation and downstream antiviral gene transcription in a dose-dependent manner,while exhibiting no effect on TNF-α-induced NF-κB signaling.pD205R targets and interacts with the intracellular domain(460-560 aa)of IFNAR1.The N-terminal region(1-76 aa)of pD205R was identified as the critical domain responsible for suppressing IFN-β-induced JAK-STAT signaling.These results demonstrate that pD205R exerts immunosuppressive effects by antagonizing IFN-β-induced JAK-STAT signaling through its interaction with the IFNAR1 intracellular domain.Collectively,this work provides mechanistic insight into pD205R's contribution to ASFV immune evasion and highlights potential targets for developing ASF vaccines and therapeutics.关键词
非洲猪瘟病毒/JAK-STAT信号通路/IFN-β/pD205R蛋白/IFNAR1Key words
African swine fever virus/JAK-STAT signaling pathway/IFN-β/pD205R/IFNAR1分类
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邵汉城,何文瑞,林志钊,范俊豪,马雨禾,訾蒙辉,潘筱雅,张雨杭,万博,张改平..非洲猪瘟病毒pD205R对JAK-STAT信号通路激活的调控作用[J].中国兽医科学,2025,55(12):1563-1573,11.基金项目
河南省自然科学基金面上项目(252300420182) （252300420182）
国家自然科学基金面上项目(32272987) （32272987）
