Interactions between Nef and AIP1 proliferate multivesicular bodies and facilitate egress of HIV-1.
Interactions between Nef and AIP1 proliferate multivesicular bodies and facilitate egress of HIV-1.
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DOI：
10.1186/1742-4690-3-33
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发表时间：
2006-06-09
期刊：
影响因子：
3.3
通讯作者：
Peterlin BM
中科院分区：
文献类型：
--
作者：
Costa LJ;Chen N;Lopes A;Aguiar RS;Tanuri A;Plemenitas A;Peterlin BM
Nef是灵长类慢病毒、HIV-1、HIV-2和SIV的辅助蛋白。除了从表面去除CD 4和MHC I类并激活细胞信号传导级联外，Nef还在病毒复制周期的后期阶段结合GagPol。在本报告中，我们进一步研究了Nef促进HIV-1复制的能力。为此，首先，在T细胞系中不存在Nef的情况下，新病毒颗粒的释放要低得多。由于在没有病毒包膜的情况下使用假型病毒获得了相同的结果，因此这种现象不依赖于CD 4和增强的感染性。接下来，我们发现Nef不仅具有AIP 1的共有基序，而且在体外和体内都能结合AIP 1。AIP 1是多泡体（MVB）形成的关键中间体，其在病毒从感染细胞的出芽和释放中起重要作用。事实上，Nef增殖细胞中的MVB，但只有当其AIP 1结合位点是完整的。最后，Nef的这些功能在原代巨噬细胞中再现，其中野生型而非突变型Nef蛋白导致新病毒颗粒从受感染细胞的释放增加。我们的结论是，通过结合GagPol和AIP 1，Nef不仅增殖MVB，而且还有助于病毒颗粒从感染细胞中排出。
Nef is an accessory protein of primate lentiviruses, HIV-1, HIV-2 and SIV. Besides removing CD4 and MHC class I from the surface and activating cellular signaling cascades, Nef also binds GagPol during late stages of the viral replicative cycle. In this report, we investigated further the ability of Nef to facilitate the replication of HIV-1. To this end, first the release of new viral particles was much lower in the absence of Nef in a T cell line. Since the same results were obtained in the absence of the viral envelope using pseudo-typed viruses, this phenomenon was independent of CD4 and enhanced infectivity. Next, we found that Nef not only possesses a consensus motif for but also binds AIP1 in vitro and in vivo. AIP1 is the critical intermediate in the formation of multivesicular bodies (MVBs), which play an important role in the budding and release of viruses from infected cells. Indeed, Nef proliferated MVBs in cells, but only when its AIP1-binding site was intact. Finally, these functions of Nef were reproduced in primary macrophages, where the wild type but not mutant Nef proteins led to increased release of new viral particles from infected cells. We conclude that by binding GagPol and AIP1, Nef not only proliferates MVBs but also contributes to the egress of viral particles from infected cells.
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