Fig. 1. Intrinsic resistance of HIV-1 CRF01_AE strains to neutralization by attachment inhibitor temsavir.
a, b The ability of temsavir to neutralize viral particles from a panel of 208 different strains was previously reported by Pancera et al.13. These data were reanalyzed with a focus on (a) the clade or (b) the identity of the polymorphic residue 375 in the Phe43 cavity of the gp120 subunit of Env (n = 208 biologically independent viral strains). Horizontal lines indicate median values. c Recombinant HIV-1 pseudoviruses expressing luciferase and bearing wild type (WT) or mutant EnvJR-FL were used to infect Cf2Th-CD4/CCR5 cells in the presence of increasing concentrations of temsavir. Infectivity at each dilution of the compound tested is shown as the percentage of infection without the compound for each particular mutant. Quadruplicate samples were analyzed in each experiment. Data shown are the means of results obtained in n = 3 independent experiments. The error bars represent the standard deviations. Neutralization half maximal inhibitory concentration (IC50) were calculated by non-linear regression using the Graphpad Prism software. d Capacity of temsavir to compete with CD4 binding as evaluated by cell-surface staining of HEK293T cells transfected with a HIV-1JR-FL Env expressor WT or its mutated counterpart. Binding of soluble CD4 (sCD4) in the presence of temsavir (10 µM) or an equal amount of DMSO was detected with the anti-CD4 OKT4 monoclonal antibody (mAb). Shown are the mean fluorescence intensities (MFI) obtained in the presence of temsavir normalized to the MFI in the absence of temsavir (DMSO) from the transfected (GFP+) population for staining obtained in n = 3 independent experiments. MFI values were normalized to the values obtained with anti-Env 2G12 mAb for each Env mutant. Error bars indicate mean ± SEM. Statistical significance was tested using a two-tailed unpaired t-test. Source data are provided as a Source Data file.