Protease-Mediated Maturation of HIV: Inhibitors of Protease and the Maturation Process

Figure 1

Proteolytic maturation of HIV-1 and its inhibition by bevirimat (BVM). (A) Gag processing cascade, illustrating the order in which the Gag precursor is cleaved by the viral protease. Each cleavage site is indicated by a scissor symbol, the red scissor symbol depicts the cleavage event blocked by BVM. (B) Virion morphology visualized by transmission electron microscopy (i, iii, v) and cryoelectron tomography models generated by segmented surface rendering. The glycoprotein spikes are coloured green, the membrane and MA layer in blue, Gag related shells in magenta, core structures in red, and other internal density in beige (ii, iv, vi). Immature particles (i and ii), mature (iii and iv), and BVM-treated (v and vi). (C) Biochemical data demonstrating accumulation of the uncleaved CA-SP1 precursor in virus particles in the presence of 1 μg/mL BVM. (D) Amino acid sequence at the CA-SP1 junction region; amino acids highlighted in green indicate the highly polymorphic residues to which reduced susceptibility to BVM in clinical trials has been mapped and amino acids highlighted in red indicate those that at which BVM resistance arises in vitro. Adapted with permission from Elsevier and the American Society for Microbiology [12, 13].