Infection of dendritic cells (DCs), not DC-SIGN-mediated internalization of human immunodeficiency virus, is required for long-term transfer of virus to T cells
Infection of dendritic cells (DCs), not DC-SIGN-mediated internalization of human immunodeficiency virus, is required for long-term transfer of virus to T cells
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DOI：
10.1128/jvi.80.6.2949-2957.2006
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发表时间：
2006-03-01
影响因子：
5.4
通讯作者：
Amara, A
中科院分区：
文献类型：
--
作者：
Burleigh, L;Lozach, PY;Amara, A
未成熟树突状细胞（DC）上表达的C型凝集素DC-SIGN捕获人类免疫缺陷病毒（HIV）颗粒并增强CD4（+）T细胞的感染。这一过程被称为 T 细胞感染的反式增强，与 HIV 内吞作用有关。有人提出，DC-SIGN 将 HIV 靶向 DC 和 DC-SIGN 表达细胞内的非降解区室，从而允许传入的病毒在感染靶细胞之前持续数天。在这项研究中，我们提供了几条证据表明完整病毒粒子的细胞内储存不会导致艾滋病毒传播。我们发现，内吞作用缺陷的 DC-SIGN 分子与野生型对应物一样有效地增强 T 细胞感染，这表明 DC-SIGN 介导的 HIV 内化对于反式增强是可有可无的。此外，利用对感染具有遗传抗性的未成熟树突状细胞，我们证明，在病毒摄取几天后，HIV从树突状细胞转移到T细胞需要病毒融合，并且仅通过树突状细胞感染和新合成的病毒颗粒的传播而发生。重要的是，我们的结果表明，DC-SIGN 通过与 HIV 进入受体合作来促进未成熟 DC 的顺式感染以及随后的病毒转移至 T 细胞，从而参与这一过程。我们认为，这种机制，而不是传入病毒的细胞内储存，解释了HIV向CD4(+)T细胞的长期转移，并可能导致DC感染的传播。
The C-type lectin DC-SIGN expressed on immature dendritic cells (DCs) captures human immunodeficiency virus (HIV) particles and enhances the infection of CD4(+) T Cells. This process, known as trans-enhancement of T-cell infection, has been related to HIV endocytosis. It has been proposed that DC-SIGN targets HIV to a nondegradative compartment within DCs and DC-SIGN-expressing cells, allowing incoming virus to persist for several days before infecting target cells. In this study, we provide several lines of evidence suggesting that intracellular storage of intact virions does not contribute to HIV transmission. We show that endocytosis-defective DC-SIGN molecules enhance T-cell infection as efficiently as their wild-type counterparts, indicating that DC-SIGN-mediated HIV internalization is dispensable for trans-enhancement. Furthermore, using immature DCs that are genetically resistant to infection, we demonstrate that several days after viral uptake, HIV transfer from DCs to T cells requires viral fusion and occurs exclusively through DC infection and transmission of newly synthesized viral particles. Importantly, our results suggest that DC-SIGN participates in this process by cooperating with the HIV entry receptors to facilitate cis-infection of immature DCs and subsequent viral transfer to T cells. We suggest that such a mechanism, rather than intracellular storage of incoming virus, accounts for the long-term transfer of HIV to CD4(+) T cells and may contribute to the spread of infection by DCs.