Cell-cell contact viral transfer contributes to HIV infection and persistence in astrocytes.
Cell-cell contact viral transfer contributes to HIV infection and persistence in astrocytes.
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DOI：
10.1007/s13365-014-0304-0
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发表时间：
2015-02
影响因子：
3.2
通讯作者：
He JJ
中科院分区：
文献类型：
--
作者：
Luo X;He JJ
星形胶质细胞是中枢神经系统中最丰富的细胞，在艾滋病毒/神经艾滋病中发挥着重要作用。在体内和体外检测到星形胶质细胞中的HIV原病毒DNA、RNA和早期基因产物，但未检测到晚期结构基因产物，表明星形胶质细胞容易受到HIV感染，尽管感染的方式受到限制。我们和其他人已经证明，无细胞的 HIV 能够通过人甘露糖受体介导的内吞作用进入 CD4− 星形胶质细胞。在这项研究中，我们利用了几种新开发的基于荧光蛋白的HIV报告病毒，并进一步表征了HIV与星形胶质细胞的相互作用。首先，我们发现HIV以细胞间接触和gp120依赖的方式成功地从HIV感染的CD4+T细胞转移到星形胶质细胞。此外，我们证明，与内吞作用介导的无细胞HIV进入和随后内吞病毒粒子的降解相比，星形胶质细胞和HIV感染的CD4+T细胞之间的细胞-细胞接触导致星形胶质细胞强烈的HIV感染，但保留了病毒基因表达的受限性质。此外，我们发现星形胶质细胞中存在艾滋病毒潜伏期。最后，我们证明感染性子代HIV很容易以细胞间接触介导的方式从HIV潜伏星形胶质细胞中回收。总而言之，我们的研究指出了细胞间接触介导的 HIV 与星形胶质细胞相互作用的重要性，并提供了直接证据来支持星形胶质细胞是中枢神经系统中的 HIV 潜在储存库的观点。
Astrocytes are the most abundant cells in the central nervous system and play important roles in HIV/neuroAIDS. Detection of HIV proviral DNA, RNA and early gene products but not late structural gene products in astrocytes in vivo and in vitro indicates that astrocytes are susceptible to HIV infection albeit in a restricted manner. We as well as others have shown that cell-free HIV is capable of entering CD4− astrocytes through human mannose receptor-mediated endocytosis. In this study, we took advantage of several newly developed fluorescence protein-based HIV reporter viruses and further characterized HIV interaction with astrocytes. First, we found that HIV was successfully transferred to astrocytes from HIV− infected CD4+ T cells in a cell-cell contact- and gp120-dependent manner. In addition, we demonstrated that compared to endocytosis-mediated cell-free HIV entry and subsequent degradation of endocytosed virions, the cell-cell contact between astrocytes and HIV-infected CD4+ T cells led to robust HIV infection of astrocytes but retained the restricted nature of viral gene expression. Furthermore, we showed that HIV latency was established in astrocytes. Lastly, we demonstrated that infectious progeny HIV was readily recovered from HIV latent astrocytes in a cell-cell contact-mediated manner. Taken together, our studies point to the importance of the cell-cell contact-mediated HIV interaction with astrocytes and provide direct evidence to support the notion that astrocytes are HIV latent reservoirs in the central nervous system.