Figure 4

The level of resistance to MVC is dependent on the efficiency of the interaction with MVC-occupied CCR5. 48 differentially induced 293-Affinofile cell populations were produced as described in Methods, and were infected with luciferase reporter viruses pseudotyped with Envs from subject 17 (A) or subject 24 (B). Infections of viruses pseudotyped with the MVC-resistant 17-Res and 24-Res Envs were also done in the presence of 10 µM MVC (lower left panels). For infections in the absence of drug, virus entry levels were normalized to entry achieved in cells expressing the highest levels of CD4 and CCR5. For infections in the presence of drug, virus entry levels were normalized to entry achieved in cells expressing the highest levels of CD4 and CCR5 in the absence of drug, as described previously [51]. 17-Sens and 24-Sens Envs were completely inhibited by MVC in the 293-Affinofile populations (data not shown). The data shown are means of duplicate infections and are representative of three independent experiments. Shaded wedges along each axis represent increasing concentrations of CD4 and CCR5, as indicated in the Methods. VERSA metrics were calculated for 17-Res (A, lower right panel) and 24-Res Env (B, lower right panel) in the absence and presence of drug, as described in Methods. The shaded wedges represent the SEM of the vector angles, and the boxes represent the SEM of the vector magnitudes.