%0 Journal Article
%T Dynamic Association between HIV-1 Gag and Membrane Domains
%A Ian B. Hogue
%A G. Nicholas Llewellyn
%A Akira Ono
%J Molecular Biology International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/979765
%X HIV-1 particle assembly is driven by the structural protein Gag. Gag binds to and multimerizes on the inner leaflet of the plasma membrane, eventually resulting in formation of spherical particles. During virus spread among T cells, Gag accumulates to the plasma membrane domain that, together with target cell membrane, forms a cell junction known as the virological synapse. While Gag association with plasma membrane microdomains has been implicated in virus assembly and cell-to-cell transmission, recent studies suggest that, rather than merely accumulating to pre-existing microdomains, Gag plays an active role in reorganizing the microdomains via its multimerization activity. In this paper, we will discuss this emerging view of Gag microdomain interactions. Relationships between Gag multimerization and microdomain association will be further discussed in the context of Gag localization to T-cell uropods and virological synapses. 1. Introduction Microdomain-based compartmentalization of the plasma membrane is implicated in many aspects of the HIV-1 life cycle. In particular, during events in the late phase of the HIV-1 life cycle such as assembly and cell-to-cell transmission, these microdomains have been thought to serve as preformed platforms that facilitate concentration of viral components (e.g., Gag and Env) or delivery of these proteins to specific locations in cells. However, recent studies suggest that Gag is not a simple passenger of microdomains but rather plays an active role in reorganizing microdomains via its membrane-binding and multimerization activities. In this paper, we focus on recent findings on this active role played by Gag during microdomain association. In light of this new view, we will also discuss the implications of plasma membrane microdomains and large-scale domains in cell-to-cell transmission. Microdomains are also thought to affect virion infectivity, attachment of virions to target cells, and virus-cell fusion, in which they modulate distributions and/or activities of Env, Nef, and virus receptors. For these topics, interested readers are referred to more comprehensive papers published in recent years [1¨C5]. 2. HIV-1 Assembly at the Plasma Membrane The viral structural polyprotein Gag is necessary and sufficient for the assembly of virus-like particles. HIV-1 Gag is synthesized as a 55£¿kDa polyprotein composed of 4 major structural domains (and 2 spacer polypeptides), as defined by cleavage by the viral protease: matrix (MA), capsid (CA), nucleocapsid (NC), and p6. However, proteolytic cleavage occurs largely after
%U http://www.hindawi.com/journals/mbi/2012/979765/