Fackler O T, Peterlin B M
Howard Hughes Medical Institute, Department of Medicine, University of California at San Francisco, 94143-0703, USA.
Curr Biol. 2000 Aug 24;10(16):1005-8. doi: 10.1016/s0960-9822(00)00654-0.
Enveloped viruses enter target cells by membrane fusion or endocytosis. In the latter case, fusion of the viral envelope is induced by the acidic pH of the endocytic vesicle [1]. As with most other retroviruses, entry of the human immunodeficiency virus (HIV) is thought to be exclusively by pH-independent membrane fusion after interaction of its envelope with CD4 and a chemokine co-receptor on the target cell [2,3]. Expression of CD4 on the virus-producing cell impairs the release and infectivity of HIV-1(NL4-3) particles [4-6]. In sharp contrast, we found that the infectivity of another HIV isolate, HIV-1SF2, was enhanced by expression of CD4 on the producer cells, which correlated with significantly increased amounts of viral proteins in the vesicular fraction of target cells. Endocytic inhibitors decreased infectivity of HIV-1SF2 but enhanced that of HIV-1 NL4-3. Expression of CD4 in the producer cell did not remove gp41 from HIV-1SF2 virions. With these cells, the formation of syncytia could be induced by acidic medium. Thus, HIV-1SF2 can enter the cytoplasm by an endocytic route after activation of gp41 by the acidic pH of endocytic vesicles. Endocytic entry might expand the range of cells that HIV could infect and should be considered in antiviral strategies against AIDS.
包膜病毒通过膜融合或内吞作用进入靶细胞。在后一种情况下，内吞囊泡的酸性pH值可诱导病毒包膜发生融合[1]。与大多数其他逆转录病毒一样，人们认为人类免疫缺陷病毒（HIV）在其包膜与靶细胞上的CD4和趋化因子共受体相互作用后，仅通过不依赖pH值的膜融合进入细胞[2,3]。在病毒产生细胞上表达CD4会损害HIV-1（NL4-3）颗粒的释放和感染性[4-6]。与之形成鲜明对比的是，我们发现，在病毒产生细胞上表达CD4可增强另一种HIV分离株HIV-1SF2的感染性，这与靶细胞囊泡部分中病毒蛋白量的显著增加相关。内吞抑制剂可降低HIV-1SF2的感染性，但可增强HIV-1 NL4-3的感染性。在病毒产生细胞中表达CD4并不会从HIV-1SF2病毒粒子中去除gp41。对于这些细胞，酸性培养基可诱导多核巨细胞的形成。因此，HIV-1SF2在通过内吞囊泡的酸性pH值激活gp41后，可通过内吞途径进入细胞质。内吞进入可能会扩大HIV可感染的细胞范围，在抗艾滋病的抗病毒策略中应予以考虑。
