3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells
3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells
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DOI：
10.1073/pnas.1003040107
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发表时间：
2010-07-27
影响因子：
11.1
通讯作者：
Subramaniam, Sriram
中科院分区：
文献类型：
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作者：
Felts, Richard L.;Narayan, Kedar;Subramaniam, Sriram
当病毒通过称为病毒学突触的特殊结构在CD4(+)T细胞和携带病毒的抗原呈递细胞(如巨噬细胞或树突状细胞)之间的结合处传递时，艾滋病毒感染的效率大大提高。利用离子磨损扫描电子显微镜、电子断层扫描和超分辨光学显微镜，我们分析了细胞-细胞接触的空间结构以及成熟树突状细胞和T细胞之间形成的病毒学突触上HIV病毒粒子的分布。我们证明了T细胞被来自成熟树突状细胞的片状膜延伸所包裹，导致形成病毒学突触的屏蔽区。在突触内，从CD4(+)T细胞发出的丝状突起使其与树突状细胞中隔离在表面可达间隔的3D网络中的HIV病毒粒子接触。在树突状细胞和T细胞的膜表面都可以检测到病毒，但病毒粒子并不是在突触处被动释放的；相反，病毒的转移需要T细胞CD4受体的参与。T细胞与细胞外环境的相对隔离，艾滋病毒转移部位的埋葬，以及T细胞对病毒粒子转移的受体依赖启动，突出了细胞间艾滋病毒传播的独特方面。
The efficiency of HIV infection is greatly enhanced when the virus is delivered at conjugates between CD4(+) T cells and virus-bearing antigen-presenting cells such as macrophages or dendritic cells via specialized structures known as virological synapses. Using ion abrasion SEM, electron tomography, and superresolution light microscopy, we have analyzed the spatial architecture of cell-cell contacts and distribution of HIV virions at virological synapses formed between mature dendritic cells and T cells. We demonstrate the striking envelopment of T cells by sheet-like membrane extensions derived from mature dendritic cells, resulting in a shielded region for formation of virological synapses. Within the synapse, filopodial extensions emanating from CD4(+) T cells make contact with HIV virions sequestered deep within a 3D network of surface-accessible compartments in the dendritic cell. Viruses are detected at the membrane surfaces of both dendritic cells and T cells, but virions are not released passively at the synapse; instead, virus transfer requires the engagement of T-cell CD4 receptors. The relative seclusion of T cells from the extracellular milieu, the burial of the site of HIV transfer, and the receptor-dependent initiation of virion transfer by T cells highlight unique aspects of cell-cell HIV transmission.