Evaluation of PRO 2000, CS, T-PSS, PMHS and SAMMA as inhibitors of HIV-1 Env-induced, CD4-dependent cell-cell fusion

Fusion of viral or HIV-infected cell membranes with susceptible target cells is mediated via the envelope glycoprotein gp120, and is an essential step in transmission. Five polyanionic candidate microbicides---SAMMA, PRO 2000, T-PSS, CS and PMHS---were tested as potential inhibitors of receptor-specific cell-cell fusion (CCF). This CCF assay possesses the following features: a transiently transfected cell line expressing the R5 HIV-1 envelope and a stable cell-line expressing the X4 HIV-1 envelope, a CD4/CCR5/CXCR4-expressing target cell line and a luciferase reporter system. SAMMA, PRO 2000 and PMHS achieved >90% inhibition of fusion at concentration of 100 mug/ml, with SAMMA exhibiting the most consistent inhibition profile. T-PSS and CS did not effectively inhibit cell-cell fusion in either R5 or X4 fusion model. In addition, intrinsic differences between the R5 and X4 glycoprotein variants were observed to play a role in inhibition of cell-cell fusion.