In vitro inhibitory effect of maraviroc on the association of the simian immunodeficiency virus envelope glycoprotein with CCR5.

Abstract

Asian macaques infected with simian immunodeficiency viruses (SIVs) isolated from African non-human primates develop a disease similar to human AIDS. SIV enters its target cells by binding to CD4 and a coreceptor, typically CCR5. Maraviroc is an entry inhibitor of human immunodeficiency virus type 1 (HIV-1) that prevents the interaction between CCR5 and the surface subunit gp120 of the viral envelope glycoprotein (Env). Thus far, the activity of maraviroc on SIV entry has been poorly studied. Here, we determined in vitro pharmacological parameters of the effect of maraviroc on the SIV Env association with CCR5. Cell-to-cell fusion inhibition assays were used to compare the susceptibility to maraviroc of the SIVsmmPBj Env-CCR5 interaction with that of HIV-1BaL Env. Analysis of dose-response curves and determination of IC50 values demonstrate that increasing concentrations of maraviroc inhibit the membrane fusion activity of SIVsmmPBj Env in a manner and to an extent similar to that of HIV-1BaL Env.