宿主和病毒的F-Box蛋白在病毒感染过程中作用的研究进展  

Research progress in role of host and viral F-Box proteins in process of viral infection

作　　者：许明秀 桓晨 XU Mingxiu;HUAN Chen(Institute of Virology and AIDS Research,First Hospital,Jilin University,Changchun 130021,China)

机构地区：[1]吉林大学第一医院艾滋病与病毒研究所,吉林长春130021

出　　处：《吉林大学学报(医学版)》2025年第1期245-254,共10页Journal of Jilin University:Medicine Edition

基　　金：国家自然科学基金面上项目(82372239);吉林省科技厅自然科学基金项目(20210101300JC);吉林省科技厅分子病毒学重点实验室项目(20102209)。

摘　　要：F-Box蛋白家族是一类含有F-Box结构域的蛋白,与细胞S期激酶相关蛋白1(SKP1)、Cullin1和环框蛋白1(RBX1)共同形成SKP1-CUL1-F-Box(SCF)E3泛素连接酶复合物,该复合物介导底物发生泛素化修饰并经蛋白酶体途径降解。宿主F-Box蛋白在整个病毒感染周期中发挥关键作用。F-Box蛋白能够调控人类免疫缺陷病毒(HIV)-1和EB病毒(EBV)等多种RNA病毒及DNA病毒的复制,且调控机制均不同。在病毒进入宿主细胞后,宿主F-Box蛋白可以调控病毒复制过程中关键蛋白质的稳定性和降解,也可增强病毒感染后宿主细胞的免疫应答,抑制病毒复制。部分F-Box蛋白能通过降解宿主限制因子、抑制病毒激活和干扰素信号通路等方式协助病毒完成复制周期。病毒也可通过编码含F-Box结构域的蛋白与宿主SKP1、Cullin1和RBX1蛋白结合,降解宿主因子促进自身复制。F-Box蛋白调控在病毒感染过程中发挥的作用差异较大,一种F-Box蛋白能够调控多种病毒的复制,一种病毒也能被多种F-Box蛋白所调控,现从宿主F-Box蛋白和病毒F-Box蛋白角度,对F-Box蛋白在病毒感染过程中的作用机制进行综述,探讨以F-Box蛋白作为靶点,开发新型抗病毒药物的意义及潜在价值。The F-Box protein family is one kind of proteins containing the F-Box domain,which are together with S-phase kinase associated protein 1(SKP1),Cullin1,and ring box protein 1(RBX1)to form the SKP1-CUL1-F-Box(SCF)E3 ubiquitin ligase complex;this complex mediates substrate ubiquitination modification and subsequent degradation via the proteasome pathway.The host F-Box protein plays an important role during the whole viral infection.The F-Box protein can regulate the replication of various RNA virus and DNA virus such as human immunodeficiency virus(HIV)and epstein-barrvirus(EB),and the regulation mechanisms are different.After the virus enters the host cells,the host F-Box protein can regulate the stability and degradation of the key proteins during virus replication,enhance the immune response of host cells after virus infection,and inhibit the virus replication.Some F-Box proteins can assist the virus in completing the replication cycle by degrading the host restriction factors and inhibiting the virus activation and the interferon signaling pathway.The viruses also degradade the host factors and promote their own replication by encoding proteins containing the F-Box domain to bind to host SKP1,Cullin1,and RBX1 proteins.There are significant differences in the role of F-Box protein regulation during virus infection;one F-Box protein can regulate the replication of multiple viruses,and one virus can also be regulated by multiple F-Box proteins.This study systematically reviews the role of F-Box proteins in the process of viral infection from the perspectives of host F-Box proteins and viral F-Box proteins,and further explores the significance and potential value of F-Box proteins as targets for developing novel antiviral drugs.

关 键 词：F-BOX蛋白 病毒 泛素蛋白酶体途径 S期激酶相关蛋白1 环框蛋白1 

分 类 号：R373[医药卫生—病原生物学]