MLV glycosylated-Gag is an infectivity factor that rescues Nef-deficient HIV-1
MLV glycosylated-Gag is an infectivity factor that rescues Nef-deficient HIV-1
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DOI：
10.1073/pnas.1001554107
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发表时间：
2010-05-18
影响因子：
11.1
通讯作者：
Pizzato, Massimo
中科院分区：
文献类型：
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作者：
Pizzato, Massimo
HIV-1病毒粒子的最佳感染性需要在一些生产细胞中合成HIV-1调节蛋白Nef，而不是其他细胞。对18种淋巴细胞系的调查发现，Nef在三种细胞系中被表达，每种细胞系都携带γ逆转录病毒。Nef依赖性细胞系通过来自独立细胞系的无细胞上清液或通过转染克隆的鼠白血病病毒（MLV）而呈现Nef非依赖性。对MLV缺失突变的分析确定糖基化gag（glycogag）是拯救Nef缺陷型HIV-1病毒体的因子。还证明Glycogag是淋巴细胞中产生的MLV病毒粒子的感染性所必需的。Nef和glycogag的直接比较揭示了对Env-假型和生产细胞类型的活性的相同依赖性。这两种蛋白质在细胞内共定位，并且都增加了靶细胞中病毒cDNA的产量。Nef和glycogag的功能相似性是趋同进化的一个令人信服的例子，其中两种结构无关的蛋白质提供了淋巴细胞中病毒体感染所必需的功能。
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.