HIV-1 trafficking to the dendritic cell-T-cell infectious synapse uses a pathway of tetraspanin sorting to the immunological synapse
HIV-1 trafficking to the dendritic cell-T-cell infectious synapse uses a pathway of tetraspanin sorting to the immunological synapse
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DOI：
10.1111/j.1600-0854.2005.00293.x
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发表时间：
2005-06-01
期刊：
影响因子：
4.5
通讯作者：
Piguet, V
中科院分区：
文献类型：
--
作者：
Garcia, E;Pion, M;Piguet, V
树突状细胞（Dendritic cells，DC）是HIV感染早期的重要组成部分。在这里，我们描述了HIV-1在被DC捕获并随后通过感染性突触呈递给CD 4（+）T细胞的过程中所遵循的运输途径。免疫荧光显微镜检查表明，成熟DC（mDC）中的含病毒区室共标记四跨膜蛋白CD 81、CD 82和CD 9，但几乎不含CD 63或LAMP-1。使用比率成像的pH值报告荧光病毒粒子在活的DC，我们表明，HIV-1是内化在细胞内的内吞隔室与pH值为6.2。值得注意的是，我们表明，无细胞病毒的感染性是更稳定的，在温和的酸性pH值比在中性pH值。使用电子显微镜，我们证实，HIV-1积累在细胞内空泡，含有CD 81阳性内膜，但只有部分重叠与CD 63。当允许接触T细胞时，HIV-1负载的DC将CD 81和CD 9以及内化的HIV-1重新分配到感染性突触，但不将免疫突触标记物MHC-II和T细胞受体重新分配到感染性突触。总之，我们的研究结果表明，HIV-1被内化到mDC中的非常规、非溶酶体、内吞区室中，并进一步表明HIV-1能够选择性地破坏形成DC-T细胞免疫突触所需的细胞内运输机制的组分，以促进其自身的细胞间转移和繁殖。
Dendritic cells (DCs) are essential components of the early events of HIV infection. Here, we characterized the trafficking pathways that HIV-1 follows during its capture by DCs and its subsequent presentation to CD4(+) T cells via an infectious synapse. Immunofluorescence microscopy indicates that the virus-containing compartment in mature DCs (mDCs) co-labels for the tetraspanins CD81, CD82, and CD9 but contains little CD63 or LAMP-1. Using ratio imaging of pH-reporting fluorescent virions in live DCs, we show that HIV-1 is internalized in an intracellular endocytic compartment with a pH of 6.2. Significantly, we demonstrate that the infectivity of cell-free virus is more stable at mildly acidic pH than at neutral pH. Using electron microscopy, we confirm that HIV-1 accumulates in intracellular vacuoles that contain CD81 positive internal membranes but overlaps only partially with CD63. When allowed to contact T cells, HIV-1-loaded DCs redistribute CD81, and CD9, as well as internalized HIV-1, but not the immunological synapse markers MHC-II and T-cell receptor to the infectious synapse. Together, our results indicate that HIV-1 is internalized into a non-conventional, non-lysosomal, endocytic compartment in mDCs and further suggest that HIV-1 is able to selectively subvert components of the intracellular trafficking machinery required for formation of the DC-T-cell immunological synapse to facilitate its own cell-to-cell transfer and propagation.