中国兽医科学2025,Vol.55Issue(10):1279-1290,12.DOI:10.16656/j.issn.1673-4696.2025.0191
BRD4和ZNF76协同调控非洲猪瘟病毒p30表达促进病毒复制的机制研究
Mechanism of synergistic regulation of African swine fever virus p30 expression by BRD4 and ZNF76 to promote viral replication
摘要
Abstract
This study aimed to elucidate the synergistic regulatory mechanism by which the interac-tion between host proteins BRD4 and ZNF76 modulates African swine fever virus(ASFV)replication.Using immunoprecipitation combined with mass spectrometry(IP-MS),we identified that BRD4 interacts with the host transcription-related factor ZNF76 through its bromodomain(BD1/2).Immunofluorescence assays con-firmed the nuclear colocalization of BRD4 and ZNF76.Upon ASFV infection of porcine alveolar macrophages(PAMs),both mRNA and protein levels of ZNF76 were up-regulated in a time-and dose-dependent manner,and overexpression of ZNF76 significantly enhanced viral replication.Mechanistic studies revealed that the BRD4-ZNF76 complex specifically binds to the viral early protein p30 and synergistically promotes its expression.This study is firstly to identify ZNF76 as a pro-viral replication host factor and to demonstrate that the BRD4-ZNF76 interaction facilitates ASFV replication by regulating viral protein expression.These findings provide important theoretical support for a deeper understanding of the molecular mechanisms by which ASFV hijacks host factors to facilitate its replication,and they offer a foundation for developing host-targeted antiviral strategies.关键词
非洲猪瘟病毒/BRD4/ZNF76/协同调控/p30/相互作用Key words
ASFV/BRD4/ZNF76/collaborative regulation/p30/interaction分类
农业科技引用本文复制引用
陈迎恩,赵亚茹,陈奕康,孙华林,张忠辉,杨吉飞,关贵全,殷宏,牛庆丽..BRD4和ZNF76协同调控非洲猪瘟病毒p30表达促进病毒复制的机制研究[J].中国兽医科学,2025,55(10):1279-1290,12.基金项目
国家自然科学基金项目(U24A20450,32072830) (U24A20450,32072830)
国家重点研发计划项目(2021YFD1800101) (2021YFD1800101)
甘肃省自然科学基金项目(25JRRA436) (25JRRA436)
甘肃省科技发展重大专项(22ZD6NA001) (22ZD6NA001)
甘肃省基础研究创新群体项目(22JR5RA024) (22JR5RA024)
中央公益性科研院所基本科研业务费专项(CAAS-ZDRW202409),中国农业科学院科技创新工程项目(CAAS-ASTIP-2021-LVRI) (CAAS-ZDRW202409)