HIV-1 Vpu inhibits accumulation of the envelope glycoprotein within clathrin-coated, Gag-containing endosomes.
Several viruses encode ion channels that both modulate the trafficking of envelope glycoprotein(s) and stimulate the release of virions from cells. HIV-1 Vpu enhances virion release and inhibits the endosomal accumulation of the viral structural protein Gag. We investigated whether Vpu affects the subcellular distribution of Env as well as Gag. Env and Vpu colocalized with each other, in part within the trans-Golgi network. In the absence of Vpu, Env accumulated more extensively within clathrin-coated endosomal structures. These structures had several features consistent with an endosomal viral assembly domain: they contained Gag, including proteolytically processed viral matrix protein; the tetraspanins CD63 and CD81; the adaptor protein complex AP-3; and AIP1/ALIX, a cellular cofactor for viral budding. These endosomes labelled incompletely with Env derived from the cell surface, suggesting that some Env reaches this compartment without transiting the plasma membrane. Consistent with this, endosomal accumulation of Env was not blocked by dominant-negative Eps15, an inhibitor of AP-2-mediated endocytosis. Although these data are potentially explained by greater endocytosis of mature virions in the absence of Vpu, they also raise the possibility that Vpu inhibits the transport of Env and Gag to late endosomes, leading to viral assembly at the plasma membrane.
Van Damme
Nanette
N
The San Diego Veterans Affairs Healthcare System, San Diego, CA 92121, USA.
Guatelli
John
J
D015703:Antigens, CD / Q000378:metabolism; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D060225:Tetraspanin 28; D060149:Tetraspanin 30; D054334:Viral Regulatory and Accessory Proteins / Q000032:analysis / Q000378:metabolism*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000032:analysis / Q000378:metabolism*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000032:analysis; D000086082:Viroporin Proteins
D015703:Antigens, CD; D002966:Clathrin; D054298:Human Immunodeficiency Virus Proteins; D010980:Platelet Membrane Glycoproteins; D060225:Tetraspanin 28; D060149:Tetraspanin 30; D054334:Viral Regulatory and Accessory Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; C554586:CD63 protein, human; C554798:CD81 protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins