Marin Mariana, Rose Kristine M, Kozak Susan L, Kabat David
Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L224, Portland, Oregon 97239-3098, USA.
Nat Med. 2003 Nov;9(11):1398-403. doi: 10.1038/nm946. Epub 2003 Oct 5.
The viral infectivity factor (Vif) encoded by HIV-1 neutralizes a potent antiviral pathway that occurs in human T lymphocytes and several leukemic T-cell lines termed nonpermissive, but not in other cells termed permissive. In the absence of Vif, this antiviral pathway efficiently inactivates HIV-1. It was recently reported that APOBEC3G (also known as CEM-15), a cytidine deaminase nucleic acid-editing enzyme, confers this antiviral phenotype on permissive cells. Here we describe evidence that Vif binds APOBEC3G and induces its rapid degradation, thus eliminating it from cells and preventing its incorporation into HIV-1 virions. Studies of Vif mutants imply that it contains two domains, one that binds APOBEC3G and another with a conserved SLQ(Y/F)LA motif that mediates APOBEC3G degradation by a proteasome-dependent pathway. These results provide promising approaches for drug discovery.
由人类免疫缺陷病毒1型（HIV-1）编码的病毒感染性因子（Vif）可中和在人类T淋巴细胞和几种白血病T细胞系（称为非允许细胞系）中发生的一种有效的抗病毒途径，但在其他称为允许细胞的细胞中则不然。在没有Vif的情况下，这种抗病毒途径可有效灭活HIV-1。最近有报道称，胞苷脱氨酶核酸编辑酶载脂蛋白B mRNA编辑酶催化多肽样3G（APOBEC3G，也称为CEM-15）赋予允许细胞这种抗病毒表型。在此，我们描述了相关证据，即Vif与APOBEC3G结合并诱导其快速降解，从而将其从细胞中清除，并阻止其掺入HIV-1病毒颗粒。对Vif突变体的研究表明，它包含两个结构域，一个与APOBEC3G结合，另一个带有保守的SLQ(Y/F)LA基序，该基序通过蛋白酶体依赖性途径介导APOBEC3G的降解。这些结果为药物研发提供了有前景的方法。
