Fig. 6.

DRV fails to inhibit the dimerization of the protease of a highly DRV-resistant HIV_8MIX^P51 variant. COS7 cells were transfected with a pair of plasmids encoding a full-length molecular infectious HIV-1 clone (HIV_8MIX^P51) containing CFP- or YFP-tagged PR with 14 amino acid substitutions (L10I, I15V, K20R, L24I, V32I, L33F, M36I, M46L, I54M, L63P, K70Q, V82I, I84V, and L89M) in the presence or absence of 0.1, 1, or 10 μM DRV. On day 3 after transfection, CFP^A/B ratios were determined as described in the legend to Fig. 2. HIV_NL4-3 served as a reference. Note that 0.1 and 1 μM DRV failed to block the dimerization of the protease of HIV_8MIX^P51, while the same concentration of DRV blocked protease dimerization in HIV_NL4-3. The differences between the CFP^A/B ratios in the absence of drug (CFP^{A/B_{No Drug}}) and the CFP^A/B ratios in the presence of 0.01 μM DRV (CFP^{A/B_{0.01 DRV}}), between the CFP^A/B ratios in the presence of 0.01 μM DRV (CFP^{A/B_{0.01 DRV}}) and 0.1 μM DRV (CFP^{A/B_{0.1 DRV}}), and between the CFP^A/B ratios in the presence of 0.1 μM DRV (CFP^{A/B_{0.1 DRV}}) and 1.0 μM DRV (CFP^{A/B_{1.0 DRV}}) had P values of 0.32, 0.0025, and 0.34 for HIV_NL4-3, respectively. The differences between the CFP^{A/B_{No Drug}} and the CFP^{A/B_{0.1 DRV}}, between the CFP^{A/B_{0.1 DRV}} and CFP^{A/B_{1.0 DRV}}, and between the CFP^{A/B_{1.0 DRV}} and the CFP^{A/B_{10.0 DRV}} had P values of 0.42, 0.022, and 0.26, respectively, for HIV_8MIX^P51.