HIV-1 Group O Integrase Displays Lower Enzymatic Efficiency and Higher Susceptibility to Raltegravir than HIV-1 Group M Subtype B Integrase

摘要: HIV-1 group O (HIV-O) is a rare variant characterized by high number of polymorphisms, especially in the integrase coding region. As HIV-O enzymes have not previously been studied, our aim was to assess impact polymorphisms on enzyme function and susceptibility inhibitors. Accordingly, we cloned purified proteins from each clades A B, an divergent strain, M (HIV-M, subtype B), used as reference. To enzymatic integrase, carried out strand transfer 3′ processing assays with various concentrations substrate (DNA target long terminal repeats [LTR], respectively) these for inhibitors (INSTIs) cell-free tissue culture, absence or presence several INSTIs. The inhibition constant (Ki) 50% effective concentration (EC50) values were calculated integrases viruses, respectively, compared those HIV-M. results showed that displayed lower activity than did HIV-M enzyme, whereas activities similar more susceptible raltegravir (RAL) competitive culture respectively. Molecular modeling suggests two key polymorphic residues are close catalytic site, 74I 153A, may play role differences.