Paradigm Shift in the Mechanism of HIV-1 Core Biogenesis

The proteolytic cleavage of the poly-protein HIV-1 Gag, which is assembled on the surface of plasma membranes of infected cells, drives the conversion of the virus from the initial immature, non-infectious form to the functionally distinct mature, infectious form. Gag cleavage results in a series of structural changes, ultimately leading to the formation of a mature core. Current models for assembly of the mature core suggest that the cleaved HIV capsid protein (CA) nucleates in a concentration-dependent manner, and polymerizes forming the conical core in a diffusion-controlled process. These models also postulate that the core begins to grow at its narrow end, and stops growing once it reaches the membrane at the opposite end. Thus, the size of the virus itself is expected to be the primary factor that determines core size. Our findings challenge this view.