Camus Grégory, Segura-Morales Carolina, Molle Dorothee, Lopez-Vergès Sandra, Begon-Pescia Christina, Cazevieille Chantal, Schu Peter, Bertrand Edouard, Berlioz-Torrent Clarisse, Basyuk Eugenia
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (UMR 8104), Paris, France.
Mol Biol Cell. 2007 Aug;18(8):3193-203. doi: 10.1091/mbc.e06-12-1147. Epub 2007 May 30.
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-1mu 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-1mu 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-1mu. 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.
逆转录病毒的组装由Gag驱动，新生病毒颗粒通过募集形成多囊泡体内腔泡的机制从细胞中释放出来。在本研究中，我们表明网格蛋白衔接复合体AP-1参与逆转录病毒的释放。通过基因敲除或RNA干扰获得的AP-1μ缺失会减少鼠白血病病毒（MLV）和HIV-1的出芽，导致病毒在细胞培养中的传播延迟。相反，AP-1μ的过表达增强了HIV-1 Gag的释放。我们表明，AP-1复合体通过基质与AP-1μ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，与晚期内体相关的MLV Gag较少，我们的结果表明，AP-1和AP-3可能在导致Gag释放的同一途径上发挥作用。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的出芽。我们提出，AP-1通过将Gag转运到活跃出芽的细胞内位点和/或通过促进其与其他细胞伙伴的相互作用来促进Gag释放。
