The clathrin adaptor complex AP-1 binds HIV-1 and MLV Gag and facilitates their budding.
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.
Camus
Grégory
G
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (UMR 8104), Paris, France.
Segura-Morales
Carolina
C
Molle
Dorothee
D
Lopez-Vergès
Sandra
S
Begon-Pescia
Christina
C
Cazevieille
Chantal
C
Schu
Peter
P
Bertrand
Edouard
E
Berlioz-Torrent
Clarisse
C
Basyuk
Eugenia
E
D033961:Adaptor Protein Complex 1 / Q000378:metabolism*; D033963:Adaptor Protein Complex 3 / Q000378:metabolism; D033983:Adaptor Protein Complex mu Subunits / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D015683:Gene Products, gag / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D009052:Leukemia Virus, Murine / Q000502:physiology*; D051379:Mice; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D014779:Virus Replication; D000099177:Tsg101 Protein
D033961:Adaptor Protein Complex 1; D033963:Adaptor Protein Complex 3; D033983:Adaptor Protein Complex mu Subunits; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D015683:Gene Products, gag; D014157:Transcription Factors; D000099177:Tsg101 Protein