Distinct Requirements for HIV-Cell Fusion and HIV-mediated Cell-Cell Fusion
Distinct Requirements for HIV-Cell Fusion and HIV-mediated Cell-Cell Fusion
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DOI：
10.1074/jbc.m114.623181
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发表时间：
2015-03-06
影响因子：
4.8
通讯作者：
Melikyan, Gregory B.
中科院分区：
文献类型：
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作者：
Kondo, Naoyuki;Marin, Mariana;Melikyan, Gregory B.
HIV-1是通过与质膜融合还是通过与内体融合进入细胞的，这是一个积极争论的主题。HIV-1能够介导相邻细胞之间的融合，这一过程被称为“从无融合”（FFNX 10），表明这种病毒可以与质膜融合。为了比较在细胞表面发生的FTWO与通过常规进入途径的HIV-细胞融合，我们设计了一种实验方法，该方法能够在同一样品中测量这两个过程。观察到以下主要差异。首先，与靶细胞融合的病毒的一小部分参与MVO。其次，尽管HIV-1与粘附细胞的融合对肌动蛋白抑制剂不敏感，但FTWO期间的后C1）4/辅助受体结合步骤被废除。在CD 4（+）T细胞中观察到HINT-细胞融合对肌动蛋白重塑的部分依赖性，但这种效应似乎是由于病毒摄取对肌动蛋白的依赖性。第三，HIV-1 gp 41胞质尾区的缺失显著增强了病毒促进FFWO的能力，同时对病毒-细胞融合具有适度的影响。ITWO与HIV细胞融合的独特效率和肌动蛋白依赖性与以下概念一致：除了介导相邻细胞质膜之间融合的小部分颗粒外，HIV-1通过内吞途径进入。然而，我们推测，在靶细胞密度高的部位，如淋巴结，细胞与细胞的接触使HIV-1与质膜融合成为可能。
Whether HIV-1 enters cells by fusing with the plasma membrane or with endosomes is a subject of active debate. The ability of HIV-1 to mediate fusion between adjacent cells, a process referred to as "fusion-from-without" (FFNX10), shows that this virus can fuse with the plasma membrane. To compare FTWO occurring at the cell surface with HIV-cell fusion through a conventional entry route, we designed an experimental approach that enabled the measurements of both processes in the same sample. The following key differences were observed. First, a very small fraction of viruses fusing with target cells participated in MVO. Second, whereas HIV-1 fusion with adherent cells was insensitive to actin inhibitors, post-C1)4/coreceptor binding steps during FTWO were abrogated. A partial dependence of HINT-cell fusion on actin remodeling was observed in CD4(+) T cells, but this effect appeared to be due to the actin dependence of virus uptake. Third, deletion of the cytoplasmic tail of HIV-1 gp41 dramatically enhanced the ability of the virus to promote FFWO, while having a modest effect on virus-cell fusion. Distinct efficiencies and actin dependences of ITWO versus HIVcell fusion are consistent with the notion that, except for a minor fraction of particles that mediate fusion between the plasma membranes of adjacent cells, HIV-1 enters through an endocytic pathway. We surmise, however, that cell-cell contacts enabling HIV-1 fusion with the plasma membrane could be favored at the sites of high density of target cells, such as lymph nodes.