The clathrin adaptor complex AP-1 binds HIV-1 and MLV Gag and facilitates their budding
The clathrin adaptor complex AP-1 binds HIV-1 and MLV Gag and facilitates their budding
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DOI：
10.1091/mbc.e06-12-1147
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发表时间：
2007-08-01
影响因子：
3.3
通讯作者：
Basyuk, Eugenia
中科院分区：
文献类型：
--
作者：
Camus, Gregory;Segura-Morales, Carolina;Basyuk, Eugenia
逆转录病毒组装由Gag驱动，新生病毒颗粒通过招募形成多泡体腔内囊泡的机制逃离细胞。在这项研究中，我们发现网格蛋白接头复合体AP-1参与了逆转录病毒的释放。通过基因敲除或RNA干扰获得的AP-1 mu缺失减少了小鼠白血病病毒（MLV）和HIV-1的出芽，导致病毒在细胞培养中繁殖延迟。相反，AP-1 mu的过表达促进了HIV-1 Gag的释放。我们发现AP-1复合体通过基质和AP-1之间的直接相互作用促进逆转录病毒出芽。在缺乏AP-1的细胞中，MLV Gag的减少与晚期核内体有关，我们的研究结果表明AP-1和AP-3可能在导致Gag释放的同一途径上起作用。此外，我们发现AP-1与Tsg101和Nedd4.1相互作用，这两种细胞蛋白已知参与HIV-1和MLV出芽。我们认为AP-1通过将Gag转运到活跃出芽的细胞内位置和/或通过促进其与其他细胞伙伴的相互作用来促进Gag的释放。
Retroviral assembly is driven by Gag, and nascent viral particles escape cells by recruiting the machinery that forms intralumenal vesicles of multivesicular bodies. In this study, we show that the clathrin adaptor complex AP-1 is involved in retroviral release. The absence of AP-1 mu obtained by genetic knock-out or by RNA interference reduces budding of murine leukemia virus (MLV) and HIV-1, leading to a delay of viral propagation in cell culture. In contrast, overexpression of AP-1 mu enhances release of HIV-1 Gag. We show that the AP-1 complex facilitates retroviral budding through a direct interaction between the matrix and AP-1 mu. Less MLV Gag is found associated with late endosomes in cells lacking AP-1, and our results suggest that AP-1 and AP-3 could function on the same pathway that leads to Gag release. In addition, we find that AP-1 interacts with Tsg101 and Nedd4.1, two cellular proteins known to be involved in HIV-1 and MLV budding. We propose that AP-1 promotes Gag release by transporting it to intracellular sites of active budding, and/or by facilitating its interactions with other cellular partners.