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.
The clathrin adaptor complex AP-1 binds HIV-1 and MLV Gag and facilitates their budding
Camus, G.; Segura-Morales, C.; Molle, D.; Lopez-Verges, S.; Begon-Pescia, C.; Cazevieille, C.; Schu, P.; Bertrand, E.; Berlioz-Torrent, C.; Basyuk, E.
Mol Biol Cell
2007-08 / vol 18 / pages 3193-203
E06-12-1147 [pii] 10.1091/mbc.E06-12-1147
IGMM team(s) involved in this publication
Humans; Animals; Mice; Virus Replication; Protein Binding; Transcription Factors/metabolism; Mutation/genetics; Protein Transport; Rats; Hela Cells; Two-Hybrid System Techniques; DNA-Binding Proteins/metabolism; Carrier Proteins/metabolism; Adaptor Protein Complex 1/*metabolism; Adaptor Protein Complex 3/metabolism; Adaptor Protein Complex mu Subunits/metabolism; Gene Products, gag/*metabolism; HIV-1/*physiology/ultrastructure; Leukemia Virus, Murine/*physiology