Targeting of the human immunodeficiency virus type 1 envelope to the trans-Golgi network through binding to TIP47 is required for Env incorporation into virions and infectivity
Targeting of the human immunodeficiency virus type 1 envelope to the trans-Golgi network through binding to TIP47 is required for Env incorporation into virions and infectivity
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DOI：
10.1128/jvi.77.12.6931-6945.2003
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发表时间：
2003-06-01
影响因子：
5.4
通讯作者：
Berlioz-Torrent, C
中科院分区：
文献类型：
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作者：
Blot, G;Janvier, K;Berlioz-Torrent, C
在这里，我们报告说，人类免疫缺陷病毒1型（HIV-1）包膜糖蛋白主要位于跨高尔基体网络（TGN）由于跨膜gp 41糖蛋白（TMgp 41）的胞质结构域中存在的决定簇。内化分析表明，存在于细胞表面的Env返回到TGN。我们发现TMgp 41的胞质结构域结合TIP 47，TIP 47是甘露糖-6-磷酸受体从内体转运到TGN所需的蛋白质。TIP 47突变体的过表达影响了Env从内体到TGN的转运。Env向TGN的逆行转运需要存在于TMgp 41胞质结构域中的Y802 W803二芳香基序。该基序的突变消除了对TGN的靶向以及与TIP 47的相互作用。这些数据支持TIP 47与HIV-1 Env的结合促进其递送至TGN的观点。最后，我们表明，在Y802 W803基序突变的病毒感染性差，并提出了一个缺陷，在Env的掺入，支持一个模型，其中Env的逆行运输涉及在完全传染性的HIV-1生产的优化。
Here, we report that human immunodeficiency virus type 1 (HIV-1) Env glycoprotein is located mainly in the trans-Golgi network (TGN) due to determinants present in the cytoplasmic domain of the transmembrane gp41 glycoprotein (TMgp41). Internalization assays demonstrated that Env present at the cell surface returns to the TGN. We found that the cytoplasmic domain of TMgp41 binds to TIP47, a protein required for the transport of mannose-6-phosphate receptors from endosomes to the TGN. Overexpression of a mutant of TIP47 affected the transport of Env from endosomes to the TGN. Retrograde transport of Env to the TGN requires a Y802W803 diaromatic motif present in the TMgp41 cytoplasmic domain. Mutation of this motif abolished both targeting to the TGN as well as interaction with TIP47. These data support the view that binding of TIP47 to HIV-1 Env facilitates its delivery to the TGN. Lastly, we show that virus mutated in the Y802W803 motif is poorly infectious and presents a defect in Env incorporation, supporting a model in which retrograde transport of Env is implicated in the optimization of fully infectious HIV-1 production.