Geraghty R J, Panganiban A T
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
J Virol. 1993 Jul;67(7):4190-4. doi: 10.1128/JVI.67.7.4190-4194.1993.
Vpu is a 16-kDa membrane-associated phosphoprotein that is expressed from the same, singly spliced message as the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor, gp160. Previous studies suggest that Vpu functions in the late stages of viral replication, possibly in virus egression from the cell. Recently, it has been demonstrated that Vpu functions to allow gp160 to be more efficiently processed by disrupting CD4-gp160 complexes generated by transfection of HeLa cells. We show here that the lack of expression of intact Vpu results in a 90% reduction in infectious virus produced over a single round of replication from HeLa cells in the absence of CD4 expression. This reduction persists when HIV-1 particles are pseudotyped with the HIV-2 or amphotropic murine leukemia virus envelope glycoprotein. Pulse-chase analysis of HIV-1 capsid protein (p24) in the absence of CD4 and envelope glycoprotein demonstrates that the rate of virus release is reduced when Vpu is not expressed. Our findings indicate that Vpu has a function involving particle release not dependent on CD4 or envelope glycoprotein expression.
Vpu是一种16千道尔顿的膜相关磷蛋白，它与人类免疫缺陷病毒1型（HIV-1）包膜糖蛋白前体gp160由相同的单剪接信使RNA表达。先前的研究表明，Vpu在病毒复制后期发挥作用，可能参与病毒从细胞中释放。最近，有研究证明Vpu通过破坏转染HeLa细胞产生的CD4-gp160复合物，使gp160能更有效地进行加工。我们在此表明，在不表达CD4的情况下，完整Vpu的缺失导致HeLa细胞在一轮复制过程中产生的感染性病毒减少90%。当HIV-1颗粒用HIV-2或嗜双性小鼠白血病病毒包膜糖蛋白进行假型化时，这种减少仍然存在。在不存在CD4和包膜糖蛋白的情况下对HIV-1衣壳蛋白（p24）进行脉冲追踪分析表明，不表达Vpu时病毒释放速率降低。我们的研究结果表明，Vpu具有一种与颗粒释放有关的功能，且不依赖于CD4或包膜糖蛋白的表达。
