Interaction of HIV-1 Gag with the clathrin-associated adaptor AP-2

Abstract

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.

Inhibition of Early Stages of HIV-1 Assembly by INI1/hSNF5 Transdominant Negative Mutant S6

“…Several host factors influence late events, including protein complexes of the endosomal sorting pathway, such as TSG101, clathrin adaptor protein complexes (including AP-1, AP-2, and AP-3), and other proteins such as Alix and Arf (2,5,13,15,18,23,38). Interferon-induced proteins such as Tetherin affect release of virus particles after budding (28).…”

Solution Structure of Calmodulin Bound to the Binding Domain of the HIV-1 Matrix Protein

“…Several cellular proteins have been implicated in Gag intracellular trafficking, virus assembly, and Gagenvelope co-localization. These include the human adaptor protein complexes 1, 2, and 3 (13)(14)(15), tail interacting protein (16), Golgi-localized ␥-ear containing Arf-binding protein (17,18), ADP-ribosylation factor (17), the suppressor of cytokine signaling 1 (19,20), Lck (a lymphoid specific Src kinase) (21), N-ethylmaleimide-sensitive factor attachment protein receptor (22), Filamin A (23), vacuolar protein sorting-associated protein 18 (24), Mon2 (24), and Lyric (25). The majority of these proteins have been shown to play roles in Gag intracellular trafficking and/or assembly.…”

Properties and functions of the nucleocapsid protein in virus assembly

“…Gag trafficking is dependent upon host cell factors interacting mainly with the MA domain. Briefly, Gag can interact with the adaptor proteins AP1, AP2, AP3 or GGA and Arf proteins [103][104][105][106] and the inhibition or overexpression of these factors impair viral assembly by disrupting the endosomal sorting pathway. NC does not appear to have a definite role in Gag trafficking to the plasma membrane as total deletion of the NC domain of Gag does not prevent some Gag molecules from reaching the plasma membrane but they are deficient in Gag-Gag multimerization and viral assembly.…”