High level of coreceptor-independent HIV transfer induced by contacts between primary CD4 T cells
High level of coreceptor-independent HIV transfer induced by contacts between primary CD4 T cells
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DOI：
10.1074/jbc.m408547200
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发表时间：
2004-12-03
影响因子：
4.8
通讯作者：
Esté, JA
中科院分区：
文献类型：
--
作者：
Blanco, J;Bosch, B;Esté, JA
细胞间病毒传播是人类免疫缺陷病毒（HIV）传播最有效的机制之一，需要靶细胞中表达CD4和辅助受体，也可能导致合胞体形成和细胞死亡。在这里，我们表明，除了这种经典的辅助受体介导的传播之外，HIV产生细胞和缺乏适当辅助受体的初级CD4 T细胞之间的接触在没有膜融合或有效HIV复制的情况下诱导靶细胞摄取HIV颗粒。 CD4 T 细胞摄取 HIV 需要通过 gp120 与 CD4 和完整肌动蛋白细胞骨架结合介导的细胞接触。 CD4 T 细胞吸收的 HIV 抗原被快速内吞至胰蛋白酶抗性区室，从而导致 CD4 分子从细胞表面部分消失。一旦细胞接触停止，捕获的艾滋病毒就会以传染性颗粒的形式释放出来。电子显微镜显示，HIV 颗粒附着在靶细胞表面，并积聚在含有 1 - 14 个病毒粒子的大（0.5 - 1.0 μm）细胞内囊泡中，没有任何证据表明存在大量网格蛋白介导的 HIV 内吞作用。将 HIV 颗粒捕获到胰蛋白酶抗性区室中需要 CD4 的 gp120 结合位点，但与 CD4 的胞质内尾部无关。总之，我们描述了一种新的 HIV 传播机制，通过感染和未感染的原代 CD4 T 细胞的接触激活，HIV 可以利用缺乏适当辅助受体的 CD4 T 细胞作为巡回病毒库。
Cell-to-cell virus transmission is one of the most efficient mechanisms of human immunodeficiency virus (HIV) spread, requires CD4 and coreceptor expression in target cells, and may also lead to syncytium formation and cell death. Here, we show that in addition to this classical coreceptor-mediated transmission, the contact between HIV-producing cells and primary CD4 T cells lacking the appropriate coreceptor induced the uptake of HIV particles by target cells in the absence of membrane fusion or productive HIV replication. HIV uptake by CD4 T cells required cellular contacts mediated by the binding of gp120 to CD4 and intact actin cytoskeleton. HIV antigens taken up by CD4 T cells were rapidly endocytosed to trypsin-resistant compartments inducing a partial disappearance of CD4 molecules from the cell surface. Once the cellular contact was stopped, captured HIV were released as infectious particles. Electron microscopy revealed that HIV particles attached to the surface of target cells and accumulated in large (0.5 - 1.0 mum) intracellular vesicles containing 1 - 14 virions, without any evidence for massive clathrin-mediated HIV endocytosis. The capture of HIV particles into trypsin-resistant compartments required the availability of the gp120 binding site of CD4 but was independent of the intracytoplasmic tail of CD4. In conclusion, we describe a novel mechanism of HIV transmission, activated by the contact of infected and uninfected primary CD4 T cells, by which HIV could exploit CD4 T cells lacking the appropriate coreceptor as an itinerant virus reservoir.