Extracellular ATP reduces HIV-1 transfer from immature dendritic cells to CD4+ T lymphocytes.
Extracellular ATP reduces HIV-1 transfer from immature dendritic cells to CD4+ T lymphocytes.
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细胞外ATP减少了HIV-1从未成熟的树突状细胞转移到CD4+ T淋巴细胞。
DOI：
10.1186/1742-4690-5-30
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发表时间：
2008-03-28
期刊：
影响因子：
3.3
通讯作者：
Tremblay, Michel J.
中科院分区：
文献类型：
--
作者：
Barat, Corinne;Gilbert, Caroline;Imbeault, Michael;Tremblay, Michel J.
树突状细胞 (DC) 被认为是粘膜部位人类免疫缺陷病毒 1 型 (HIV-1) 感染早期事件的关键介质。先前的研究表明，在 DC 内吞液泡中发现的表面结合病毒粒子和/或内化病毒可有效转移至 CD4+ T 细胞。坏死细胞分泌或释放的细胞外三磷酸腺苷 (ATP) 会诱导 DC 的成熟扭曲，暂时增加其内吞能力并影响其迁移能力。我们知道在组织损伤和炎症的情况下存在高细胞外 ATP 浓度，因此我们研究了 ATP 对 HIV-1 从 DC 到 CD4+ T 淋巴细胞传播的影响。在这项研究中，我们发现细胞外 ATP 减少了 HIV-1 从未成熟单核细胞衍生的 DC (iDC) 向自体 CD4+ T 细胞的转移。这种观察到的病毒复制减少与转移后受感染的 CD4+ T 细胞比例较低有关，并且在 HIV-1 的 X4 和 R5 嗜性分离株中均可见。细胞外 ATP 对直接 CD4+ T 细胞感染以及 iDC 的生产性 HIV-1 感染没有影响。这些观察结果表明，细胞外 ATP 反式影响 CD4+ T 细胞的 HIV-1 感染，但对 iDC 的从头病毒生产没有影响。其他实验表明，细胞外 ATP 可能会调节 iDC 内内化病毒颗粒的运输途径，导致溶酶体降解增加，这可能是 HIV-1 传播减少的部分原因。这些结果表明细胞外 ATP 可以作为控制 HIV-1 传播的因素。
Dendritic cells (DCs) are considered as key mediators of the early events in human immunodeficiency virus type 1 (HIV-1) infection at mucosal sites. Previous studies have shown that surface-bound virions and/or internalized viruses found in endocytic vacuoles of DCs are efficiently transferred to CD4+ T cells. Extracellular adenosine triphosphate (ATP) either secreted or released from necrotic cells induces a distorted maturation of DCs, transiently increases their endocytic capacity and affects their migratory capacity. Knowing that high extracellular ATP concentrations are present in situations of tissue injury and inflammation, we investigated the effect of ATP on HIV-1 transmission from DCs to CD4+ T lymphocytes. In this study, we show that extracellular ATP reduces HIV-1 transfer from immature monocyte-derived DCs (iDCs) to autologous CD4+ T cells. This observed decrease in viral replication was related to a lower proportion of infected CD4+ T cells following transfer, and was seen with both X4- and R5-tropic isolates of HIV-1. Extracellular ATP had no effect on direct CD4+ T cell infection as well as on productive HIV-1 infection of iDCs. These observations indicate that extracellular ATP affects HIV-1 infection of CD4+ T cells in trans with no effect on de novo virus production by iDCs. Additional experiments suggest that extracellular ATP might modulate the trafficking pathway of internalized virions within iDCs leading to an increased lysosomal degradation, which could be partly responsible for the decreased HIV-1 transmission. These results suggest that extracellular ATP can act as a factor controlling HIV-1 propagation.
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