吉林大学学报(医学版)

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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

许明秀,桓晨()   

  1. 吉林大学第一医院艾滋病与病毒研究所,吉林 长春 130021
  • 收稿日期:2023-10-13 出版日期:2024-06-06 发布日期:2024-06-06
  • 通讯作者: 桓晨 E-mail:lmsxsml@jlu.edu.cn
  • 作者简介:许明秀(1999-),女,山东省济南市人,在读硕士研究生,主要从事病毒与宿主相互关系方面的研究。
  • 基金资助:
    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)

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

Mingxiu XU,Chen HUAN()   

  1. AIDS and Virus Research Institute,First Hospital,Jilin University,Changchun 130021,China
  • Received:2023-10-13 Online:2024-06-06 Published:2024-06-06
  • Contact: Chen HUAN E-mail:lmsxsml@jlu.edu.cn

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、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)在内的多种RNA病毒和DNA病毒的复制,且调控机制均有所不同。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,也可以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。病毒也可以通过编码含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和潜在价值。

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

Abstract:

The F-Box protein family is one kind of proteins containing the F-Box domain, which were 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 cell, 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 degrade the host restriction factors, inhibit the virus activation, interfere with the interferon signaling pathway, and assist the virus in completing the replication cycle. The viruses also promote their own replication by encoding proteins containing the F-Box domain to bind to host SKP1, Cullin1, and RBX1 proteins for degradation of host factors. 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.

Key words: F-Box protein, Virus, Ubiquitin-Proteasome pathway, S-phase kinase-associated protein 1, Ring box protein 1

中图分类号: 

  • R373