Henderson Hamani I, Hope Thomas J
University of Illinois @ Chicago, Department of Microbiology and Immunology, Chicago, IL 60612, USA.
Virol J. 2006 May 25;3:36. doi: 10.1186/1743-422X-3-36.
HIV entry occurs via membrane-mediated fusion of virus and target cells. Interactions between gp120 and cellular co-receptors lead to both the formation of fusion pores and release of the HIV genome into target cells. Studies using cell-cell fusion assays have demonstrated that a temperature-arrested state (TAS) can generate a stable intermediate in fusion related events. Other studies with MLV pseudotyped with HIV envelope also found that a temperature sensitive intermediate could be generated as revealed by the loss of a fluorescently labeled membrane. However, such an intermediate has never been analyzed in the context of virus infection. Therefore, we used virus-cell infection with replication competent HIV to gain insights into virus-cell fusion. We find that the TAS is an intermediate in the process culminating in the HIV infection of a target cell. In the virion-cell TAS, CD4 has been engaged, the heptad repeats of gp41 are exposed and the complex is kinetically predisposed to interact with coreceptor to complete the fusion event leading to infection.
HIV通过病毒与靶细胞的膜介导融合进入细胞。gp120与细胞共受体之间的相互作用导致融合孔的形成以及HIV基因组释放到靶细胞中。使用细胞-细胞融合试验的研究表明，温度阻滞状态（TAS）可在融合相关事件中产生稳定的中间体。其他用HIV包膜假型化的MLV进行的研究也发现，如通过荧光标记膜的丢失所揭示的那样，可产生温度敏感中间体。然而，从未在病毒感染的背景下分析过这种中间体。因此，我们使用具有复制能力的HIV进行病毒-细胞感染，以深入了解病毒-细胞融合。我们发现TAS是最终导致HIV感染靶细胞过程中的一个中间体。在病毒体-细胞TAS中，CD4已结合，gp41的七肽重复序列暴露，并且该复合物在动力学上易于与共受体相互作用以完成导致感染的融合事件。
