Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
Proc Natl Acad Sci U S A. 2010 May 18;107(20):9364-9. doi: 10.1073/pnas.1001554107. Epub 2010 May 3.
Optimal infectivity of HIV-1 virions requires synthesis of the HIV-1 regulatory protein Nef in some producer cells but not others. A survey of 18 lymphoid cell lines found that Nef was dispensable in three, each of which harbored gammaretroviruses. Nef-dependent cell lines were rendered Nef-independent by a cell-free supernatant from the independent lines or by transfection of cloned murine leukemia virus (MLV). Analysis of MLV deletion mutations identified glycosylated gag (glycogag) as the factor that rescues Nef-defective HIV-1 virions. Glycogag was also demonstrated to be required for the infectivity of MLV virions produced in lymphoid cells. Direct comparison of Nef and glycogag revealed identical dependence for activity on Env-pseudotype and producer cell type. The two proteins colocalize within cells, and both increase the yield of viral cDNA in target cells. The functional similarity of Nef and glycogag is a compelling example of convergent evolution in which two structurally unrelated proteins provide a function necessary for virion infectivity in lymphoid cells.
HIV-1 病毒粒子的最佳感染性需要在一些产生细胞中合成 HIV-1 调节蛋白 Nef，但在其他细胞中不需要。对 18 种淋巴母细胞系的调查发现，有三种细胞系不需要 Nef，它们都携带γ逆转录病毒。无细胞上清液或通过转染克隆鼠白血病病毒 (MLV)，可使依赖 Nef 的细胞系变为非依赖 Nef。对 MLV 缺失突变的分析表明，糖基化 gag（glycogag）是拯救 Nef 缺陷型 HIV-1 病毒粒子的因子。还证明糖基化 gag 对于在淋巴母细胞中产生的 MLV 病毒粒子的感染性是必需的。Nef 和 glycogag 的直接比较表明，活性对 Env-假型和产生细胞类型的依赖性相同。这两种蛋白在细胞内共定位，并且都增加了靶细胞中病毒 cDNA 的产量。Nef 和 glycogag 的功能相似是趋同进化的一个令人信服的例子，其中两种结构上不相关的蛋白提供了在淋巴母细胞中病毒粒子感染性所必需的功能。
