摘要
非洲猪瘟(ASF)是由非洲猪瘟病毒(ASFV)引起的烈性动物传染病,该病具有高传染性和极高致死率的特点,对全球养猪业构成严重威胁。随着对ASFV的不断深入研究,发现ASFV在转录和翻译层面可通过编码多种病毒蛋白发挥基因表达调控作用,促进病毒自身复制。在转录层面,ASFV通过一系列机制系统性抑制宿主转录,包括抑制宿主m RNA的合成、促进其降解、介导其脱帽、通过异常加尾破坏其稳定性、阻止其出核,甚至通过破坏细胞核结构来实现全局性调控。在翻译层面,ASFV展现出精密的时序调控能力。在感染早期,它可以通过去磷酸化真核翻译起始因子2α(eIF2α)以维持eIF2活性,从而增强宿主蛋白合成,为病毒复制提供物质基础,而在感染后期,则可能通过磷酸化eIF2α来抑制特定宿主蛋白的合成,将细胞资源彻底转向病毒蛋白的生产。ASFV还可通过调控eIF4F复合体组装以影响翻译过程,在感染的不同时期改变eIFs定位,将宿主翻译机器劫持至病毒工厂,利用RNA甲基转移酶稳定核糖体RNA,防止病毒蛋白合成关闭。这些机制揭示了ASFV系统性重塑宿主细胞内环境的综合策略,为研发针对关键病毒蛋白、宿主因子以及病毒工厂组装过程的抗病毒药物和减毒活疫苗提供了重要的理论依据。
African swine fever(ASF)is a highly pathogenic,contagious,and lethal animal infectious disease caused by the African swine fever virus(ASFV),posing a severe threat to the global swine industry.Recent in-depth studies on ASFV have revealed that the virus regulates host gene expression at transcriptional and translational levels through encoding multiple viral proteins to facilitate its own replication.At the transcriptional level,ASFV suppresses host transcription by inhibiting host mRNA synthesis,promoting host mRNA degradation,inducing host mRNA decapping,destabilizing host mRNA via aberrant polyadenylation,blocking host mRNA nuclear export,and even induction of nuclear structure disruption to achieve overall transcriptional regulation.At the translational level,ASFV demonstrates sophisticated temporal regulation.During early infection,ASFV maintains eIF2 activity by dephosphorylating eIF2αto enhance host protein synthesis,thereby providing the material basis for viral replication.In later stages,however,it may suppress the synthesis of specific host proteins by phosphorylating eIF2α,thereby redirecting cellular resources entirely toward viral protein production.Additionally,ASFV can modulate translation by regulating eIF4F complex assembly,altering the subcellular localization of eukaryotic initiation factors(eIFs)at different infection stage,hijack the host translation machinery into viral factories,and stabilize ribosomal RNA via RNA methyltransferases to prevent shutdown of viral protein synthesis.These mechanisms illustrate ASFV's systematic strategy to remodel the host intracellular environment,providing an important theoretical foundation for developing antiviral drugs and live attenuated vaccines targeting key viral proteins,host factors,and the assembly process of viral factories.
作者
孙筱弈
李洋
朱紫祥
SUN Xiaoyi;LI Yang;ZHU Zixiang(College of Veterinary Medicine of Lanzhou University,Lanzhou 730000,China;National Foot-and Mouth Diseases Reference Laboratory/State Key Laboratory of Animal Disease Control and Prevention/Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Lanzhou 730046,China)
出处
《中国兽医科学》
北大核心
2026年第2期241-247,共7页
Chinese Veterinary Science
基金
“十四五”广东省农业科技创新十大主攻方向“揭榜挂帅”项目(2024KJ14)
甘肃省科技专项(24JRRA813,25JRRA1120,24JRRA804,23JRRA546)
国家生猪产业技术体系项目(CARS-35)
国家生猪技术创新中心项目(NCTIP-XD/C03)。
关键词
非洲猪瘟病毒
调控
转录
翻译
African swine fever virus
regulation
transcription
translation
