Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages.
Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages.
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DOI：
10.1083/jcb.201201144
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发表时间：
2012-10-29
期刊：
影响因子：
--
通讯作者：
Benaroch P
中科院分区：
文献类型：
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作者：
Gaudin R;de Alencar BC;Jouve M;Bèrre S;Le Bouder E;Schindler M;Varthaman A;Gobert FX;Benaroch P
KIF3A 对于含有 HIV 的区室的细胞内运输和受感染的巨噬细胞释放 HIV 非常重要。巨噬细胞是 HIV 感染的长寿命靶细胞，被认为是病毒储存库。巨噬细胞中的 HIV 组装发生在含有病毒的区室 (VCC) 中，病毒粒子在其中积累和储存。这些 VCC 的贩运和释放的监管仍然未知。使用 HIV-1 感染的原代人类巨噬细胞的高分辨率光学和电子显微镜，我们发现 VCC 的空间分布取决于微管网络，并且 VCC 限制膜与 KIF3A+ 微管密切相关。沉默 KIF3A 会显着降低 HIV-1 感染巨噬细胞的病毒释放，导致 VCC 在细胞内积累。延时显微镜进一步表明 VCC 和相关的 KIF3A 沿着微管一起移动。重要的是，KIF3A 在不具有 VCC 的 T 细胞释放 HIV 的过程中不起作用。这些结果表明，HIV-1 需要分子马达 KIF3 才能在初级巨噬细胞中完成其循环。针对这一步骤可能会产生消除这种病毒库的新策略。
KIF3A is important for the intracellular transport of HIV-containing compartments and HIV release from infected macrophages. Macrophages are long-lived target cells for HIV infection and are considered viral reservoirs. HIV assembly in macrophages occurs in virus-containing compartments (VCCs) in which virions accumulate and are stored. The regulation of the trafficking and release of these VCCs remains unknown. Using high resolution light and electron microscopy of HIV-1–infected primary human macrophages, we show that the spatial distribution of VCCs depended on the microtubule network and that VCC-limiting membrane was closely associated with KIF3A+ microtubules. Silencing KIF3A strongly decreased virus release from HIV-1–infected macrophages, leading to VCC accumulation intracellularly. Time-lapse microscopy further suggested that VCCs and associated KIF3A move together along microtubules. Importantly, KIF3A does not play a role in HIV release from T cells that do not possess VCCs. These results reveal that HIV-1 requires the molecular motor KIF3 to complete its cycle in primary macrophages. Targeting this step may lead to novel strategies to eliminate this viral reservoir.