Tail-interacting protein TIP47 is a connector between Gag and Env and is required for Env incorporation into HIV-1 virions
Tail-interacting protein TIP47 is a connector between Gag and Env and is required for Env incorporation into HIV-1 virions
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DOI：
10.1073/pnas.0602941103
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发表时间：
2006-10-03
影响因子：
11.1
通讯作者：
Berlioz-Torrent, Clarisse
中科院分区：
文献类型：
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作者：
Lopez-Verges, Sandra;Camus, Gregory;Berlioz-Torrent, Clarisse
HIV-1病毒粒子中包膜糖蛋白Env的存在对于传染性是必不可少的。到目前为止，Env被包装成病毒粒子的分子机制在很大程度上还不清楚。在这里，我们发现TIP47(47 kDa的尾部相互作用蛋白)也与HIV-1 Gag蛋白的MA(基质)结构域结合，这三种蛋白形成一个三元复合体。与TIP47相互作用的Gag突变抑制了Env的掺入和病毒粒子的感染性，以及Gag和Env之间的共存。我们还表明，沉默TIP47会损害Env的掺入和感染性，并取消GAG与Env的免疫共沉淀。相反，TIP47的过表达增加了Env包装。最后，我们证明了TIP47可以同时与Env和GAG相互作用。综上所述，我们的结果表明，TIP47是一种细胞辅助因子，在Env的掺入过程中起着至关重要的作用，允许HIV-1 Gag和Env蛋白在病毒组装过程中相遇和物理结合。
The presence of the envelope glycoprotein Env in HIV-1 virions is essential for infectivity. To date, the molecular mechanism by which Env is packaged into virions has been largely unknown. Here, we show that TIP47 (tail-interacting protein of 47 kDa), which has been shown to interact with Env, also binds the MA (matrix) domain of HIV-1 Gag protein and that these three proteins form a ternary complex. Mutations in Gag that abrogate interaction with TIP47 inhibit Env incorporation and virion infectivity as well as colocalization between Gag and Env. We also show that TIP47 silencing impairs Env incorporation and infectivity and abolishes coimmunoprecipitation of Gag with Env. In contrast, overexpression of TIP47 increases Env packaging. Last, we demonstrate that TIP47 can interact simultaneously with Env and Gag. Taken together, our results show that TIP47 is a cellular cofactor that plays an essential role in Env incorporation, allowing the encounter and the physical association between HIV-1 Gag and Env proteins during the viral assembly process.