Interaction of HIV-1 Gag with the clathrin-associated adaptor AP-2.
The envelope glycoprotein (Env) of HIV-1 interacts with the clathrin-associated adaptor complex AP-2 during the late phase of the viral replication cycle. Upon its synthesis, Env, therefore, is retrieved from the cellular surface unless internalization is inhibited by viral Gag. Here we demonstrate that not only Env, but also HIV-1 Gag, specifically binds to AP-2. Gag-AP-2 association was found to depend on tyrosine residue 132 and valine residue 135 at the matrix-capsid junction in the Gag polyprotein. Results of a morphological analysis of viral egress from cells expressing dominant-negative AP-2 suggest an involvement of AP-2 in confining HIV-1 exit to distinct microdomains. Further, particle release from AP-2-mutant cells was enhanced compared to release from wild-type cells but the infectivity of virus released from these cells was moderately reduced. Together these data attribute a role to the AP-2 complex in the regulation of HIV-1 assembly/release.
Batonick
Melissa
M
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
Favre
Manuel
M
Boge
Michael
M
Spearman
Paul
P
Höning
Stefan
S
Thali
Markus
M
D033962:Adaptor Protein Complex 2 / Q000378:metabolism*; D015536:Down-Regulation; D015683:Gene Products, gag / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D014443:Tyrosine / Q000502:physiology; D014633:Valine / Q000502:physiology; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus
D033962:Adaptor Protein Complex 2; D015683:Gene Products, gag; D054301:gag Gene Products, Human Immunodeficiency Virus; C083868:gag protein p1, Human immunodeficiency virus; D014443:Tyrosine; D014633:Valine