The temperature arrested intermediate of virus-cell fusion is a functional step in HIV infection.
The temperature arrested intermediate of virus-cell fusion is a functional step in HIV infection.
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DOI：
10.1186/1743-422x-3-36
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发表时间：
2006-05-25
期刊：
影响因子：
4.8
通讯作者：
Hope TJ
中科院分区：
文献类型：
--
作者：
Henderson HI;Hope TJ
HIV通过病毒和靶细胞的膜介导融合进入。gp 120和细胞共受体之间的相互作用导致融合孔的形成和HIV基因组释放到靶细胞中。使用细胞-细胞融合测定的研究已经证明，温度停滞状态（TAS）可以在融合相关事件中产生稳定的中间体。使用HIV包膜进行MLV假型化的其他研究也发现，可以产生温度敏感性中间体，如荧光标记膜的丢失所示。然而，这种中间体从未在病毒感染的情况下进行过分析。因此，我们使用具有复制能力的HIV的病毒-细胞感染来深入了解病毒-细胞融合。我们发现TAS是最终导致HIV感染靶细胞的过程中的中间体。在病毒体细胞TAS中，CD 4已经被接合，gp 41的七肽重复被暴露，并且复合物在动力学上倾向于与辅助受体相互作用以完成导致感染的融合事件。
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.