Dendritic cells (DCs) are one of the earliest targets of HIV-1 infection acting as a "Trojan horse," concealing the virus from the innate immune system and delivering it to T cells via virological synapses (VS). To explicate how the virus is trafficked through the cell to the VS and evades degradation, a high-throughput small interfering RNA screen targeting membrane trafficking proteins was performed in monocyte-derived DCs. We identified several proteins including BIN-1 and RAB7L1 that share common roles in transport from endosomal compartments. Depletion of target proteins resulted in an accumulation of virus in intracellular compartments and significantly reduced viral trans-infection via the VS. By targeting endocytic trafficking and retromer recycling to the plasma membrane, we were able to reduce the virus's ability to accumulate at budding microdomains and the VS. Thus, we identify key genes involved in a pathway within DCs that is exploited by HIV-1 to traffic to the VS.IMPORTANCE The lentivirus human immunodeficiency virus (HIV) targets and destroys CD4+ T cells, leaving the host vulnerable to life-threatening opportunistic infections associated with AIDS. Dendritic cells (DCs) form a virological synapse (VS) with CD4+ T cells, enabling the efficient transfer of virus between the two cells. We have identified cellular factors that are critical in the induction of the VS. We show that ADP-ribosylation factor 1 (ARF1), bridging integrator 1 (BIN1), and Rab GTPases RAB7L1 and RAB8A are important regulators of HIV-1 trafficking to the VS and therefore the infection of CD4+ T cells. We found these cellular factors were essential for endosomal protein trafficking and formation of the VS and that depletion of target proteins prevented virus trafficking to the plasma membrane by retaining virus in intracellular vesicles. Identification of key regulators in HIV-1 trans-infection between DC and CD4+ T cells has the potential for the development of targeted therapy to reduce trans-infection of HIV-1 in vivo.

中文翻译：

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树突状细胞中HIV-1病毒突触形成所需的宿主运输基因的鉴定。

树突状细胞（DC）是HIV-1感染的最早目标之一，充当“特洛伊木马”，将病毒从先天免疫系统中隐藏起来，并通过病毒突触（VS）传递给T细胞。为了说明病毒如何通过细胞运输到VS并逃避降解，在单核细胞衍生的DC中进行了针对膜运输蛋白的高通量小干扰RNA筛选。我们鉴定了包括BIN-1和RAB7L1在内的几种蛋白质，它们在从内体区室转运中具有共同的作用。靶蛋白的耗尽导致病毒在细胞内区室中积累，并显着减少了通过VS进行的病毒转染。通过针对内吞运输和后体回收到质膜，我们能够减少病毒的 在萌芽的微域和VS上积累的能力。因此，我们确定了DC中被HIV-1利用以通向VS的通路中涉及的关键基因。重要慢病毒人类免疫缺陷病毒（HIV）靶向并破坏CD4 + T细胞，使宿主容易受到威胁生命的机会与艾滋病相关的感染。树突状细胞（DC）与CD4 + T细胞形成病毒突触（VS），可在两个细胞之间有效转移病毒。我们已经确定了诱导VS至关重要的细胞因子。我们显示，ADP-核糖基化因子1（ARF1），桥整合子1（BIN1）和Rab GTPases RAB7L1和RAB8A是HIV-1向VS转运的重要调节剂，因此感染CD4 + T细胞。我们发现这些细胞因子对于内体蛋白运输和VS的形成至关重要，并且靶蛋白的耗尽通过将病毒保留在细胞内囊泡中阻止了病毒向质膜的运输。鉴定DC和CD4 + T细胞之间HIV-1转染中的关键调控因子具有开发靶向疗法以减少体内HIV-1转染的潜力。