Abstract

The plasma membrane (PM) is a physical barrier that must be breached when pathogens like HIV enter and exit cells. In most cell types, HIV egress begins when the structural Gag protein binds and assembles on the inner leaflet of the PM (Fig. 1). Gag assembly distends the membrane into a spherical virion that is released by a membrane fission reaction catalyzed by the cellular endosomal sorting complexes required for transport (ESCRT) machinery (1). HIV must therefore target the PM selectively to avoid futile release into intracellular compartments. Previous studies have revealed important aspects of the targeting mechanism (2, 3), but the pathway is not yet fully understood. A study in PNAS by Dick et al. takes us a step closer to that goal by showing that HIV Gag can discriminate between membranes with different cholesterol and fatty acid compositions, thereby helping to explain how viral assembly can be targeted to lipid rafts on the PM (4).

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