Yu Xianghui, Yu Yunkai, Liu Bindong, Luo Kun, Kong Wei, Mao Panyong, Yu Xiao-Fang
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Science. 2003 Nov 7;302(5647):1056-60. doi: 10.1126/science.1089591. Epub 2003 Oct 16.
Human immunodeficiency virus-1 (HIV-1) Vif is essential for viral evasion of host antiviral factor CEM15/APOBEC3G. We report that Vif interacts with cellular proteins Cul5, elongins B and C, and Rbx1 to form an Skp1-cullin-F-box (SCF)-like complex. The ability of Vif to suppress antiviral activity of APOBEC3G was specifically dependent on Cul5-SCF function, allowing Vif to interact with APOBEC3G and induce its ubiquitination and degradation. A Vif mutant that interacted with APOBEC3G but not with Cul5-SCF was functionally inactive. The Cul5-SCF was also required for Vif function in distantly related simian immunodeficiency virus mac. These results indicate that the conserved Cul5-SCF pathway used by Vif is a potential target for antiviral development.
人类免疫缺陷病毒1型（HIV-1）的病毒感染因子（Vif）对于病毒逃避宿主抗病毒因子CEM15/载脂蛋白B mRNA编辑酶催化多肽样3G（APOBEC3G）至关重要。我们报告称，Vif与细胞蛋白Cul5、延伸蛋白B和C以及Rbx1相互作用，形成一种类Skp1-遍在蛋白连接酶（SCF）复合物。Vif抑制APOBEC3G抗病毒活性的能力特别依赖于Cul5-SCF功能，使Vif能够与APOBEC3G相互作用并诱导其泛素化和降解。一个与APOBEC3G相互作用但不与Cul5-SCF相互作用的Vif突变体在功能上无活性。在远亲的猴免疫缺陷病毒（SIVmac）中，Cul5-SCF对于Vif功能也是必需的。这些结果表明，Vif所使用的保守的Cul5-SCF途径是抗病毒药物开发的一个潜在靶点。
