Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
J Biol Chem. 2010 Nov 12;285(46):35350-8. doi: 10.1074/jbc.M110.173286. Epub 2010 Sep 10.
Antiretroviral cytidine deaminase APOBEC3G, which is abundantly expressed in peripheral blood lymphocytes and macrophages, strongly protects these cells against HIV-1 infection. The HIV-1 Vif protein overcomes this antiviral effect by enhancing proteasome-mediated APOBEC3G degradation and is key for maintaining viral infectivity. The 579-bp-long vif gene displays high genetic diversity among HIV-1 subtypes. Therefore, it is intriguing to address whether Vif proteins derived from different subtypes differ in their viral defense activity against APOBEC3G. Expression plasmids encoding Vif proteins derived from subtypes A, B, C, CRF01_AE, and CRF02_AG isolates were created, and their anti-APOBEC3G activities were compared. Viruses produced from cells expressing APOBEC3G and Vif proteins from different subtypes showed relatively different viral infectivities. Notably, subtype C-derived Vif proteins tested had the highest activity against APOBEC3G that was ascribed to its increased binding activity, for which the N-terminal domain of the Vif protein sequences was responsible. These results suggest that the biological differences of Vif proteins belonging to different subtypes might affect viral fitness and quasispecies in vivo.
抗病毒胞苷脱氨酶 APOBEC3G 在周围血淋巴细胞和巨噬细胞中大量表达，强烈保护这些细胞免受 HIV-1 感染。HIV-1 的 Vif 蛋白通过增强蛋白酶体介导的 APOBEC3G 降解来克服这种抗病毒作用，是维持病毒感染力的关键。579bp 长的 vif 基因在 HIV-1 亚型中显示出高度的遗传多样性。因此，研究不同亚型的 Vif 蛋白在对 APOBEC3G 的病毒防御活性方面是否存在差异是很有趣的。构建了编码来自亚型 A、B、C、CRF01_AE 和 CRF02_AG 分离株的 Vif 蛋白的表达质粒，并比较了它们的抗 APOBEC3G 活性。来自表达 APOBEC3G 和来自不同亚型的 Vif 蛋白的细胞产生的病毒显示出相对不同的病毒感染力。值得注意的是，测试的来自 C 亚型的 Vif 蛋白对 APOBEC3G 的活性最高，这归因于其增加的结合活性，而 Vif 蛋白序列的 N 端结构域对此负责。这些结果表明，属于不同亚型的 Vif 蛋白的生物学差异可能影响病毒在体内的适应性和准种。
