Dynamic Association between HIV-1 Gag and Membrane Domains

Abstract

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.

Figure 1

(a) Gag accumulates at the uropod surface. While it remains to be determined whether the first contact between virus-producing and target cells occurs right at the uropod or elsewhere during VS formation, virus-laden uropods do participate in VS formation as determined by concentration of uropod markers at the VS. (b) A working model for a mechanism by which Gag multimers associate with rearward actin flow that directs Gag to the uropod. NC-dependent Gag multimerization underneath the plasma membrane promotes association between Gag multimer and UDM. Of note, in contrast to lipid raft and TEM markers, UDM proteins appear to accumulate at assembly sites of wild-type Gag as well as those of a Gag mutant that multimerizes but fails to bud (GNL, unpublished data).