Bedinger P, Moriarty A, von Borstel R C, Donovan N J, Steimer K S, Littman D R
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Nature. 1988 Jul 14;334(6178):162-5. doi: 10.1038/334162a0.
Binding of the human immunodeficiency virus (HIV) to infectable host cells, such as B and T lymphocytes, monocytes and colorectal cells, is mediated by a high-affinity interaction between the gp120 component of the viral envelope glycoprotein and the CD4 receptor. Upon binding, it is thought that the second component of the envelope, gp41, mediates fusion between the viral envelope and host cell membranes. However, the early steps of HIV infection have not yet been thoroughly elucidated. Viral entry was first reported to be mediated by pH-dependent receptor-mediated endocytosis; subsequent studies have shown entry to be pH-independent. Although direct fusion of virus to plasma membranes of infected cells has been observed by electron microscopy, it is still formally possible that the infectious path of the virus involves receptor-mediated endocytosis. To gain a better understanding of receptor function in viral entry, we have analysed the ability of several altered or truncated forms of CD4 to serve as effective viral receptors. Our results indicate that domains beyond the HIV-binding region of CD4 are not required for viral infection. Some of the altered forms of CD4 that serve as effective HIV receptors are severely impaired in their ability to be endocytosed. These experiments therefore support the notion that viral fusion to the plasma membrane is sufficient for infection.
人类免疫缺陷病毒（HIV）与可感染的宿主细胞（如B和T淋巴细胞、单核细胞及结肠直肠细胞）的结合，是由病毒包膜糖蛋白的gp120成分与CD4受体之间的高亲和力相互作用介导的。据认为，结合后，包膜的第二个成分gp41介导病毒包膜与宿主细胞膜之间的融合。然而，HIV感染的早期步骤尚未完全阐明。病毒进入最初被报道是由pH依赖的受体介导的内吞作用介导的；随后的研究表明进入是pH不依赖的。尽管通过电子显微镜观察到病毒与受感染细胞质膜的直接融合，但病毒的感染途径仍有可能涉及受体介导的内吞作用。为了更好地理解受体在病毒进入中的功能，我们分析了几种改变或截短形式的CD4作为有效病毒受体的能力。我们的结果表明，CD4的HIV结合区域之外的结构域对于病毒感染并非必需。一些作为有效HIV受体的CD4改变形式在其被内吞的能力方面严重受损。因此，这些实验支持了病毒与质膜融合足以导致感染这一观点。
