FIG. 4.

Transient replicons show lack of cross-resistance to other classes of HCV inhibitors. Huh7-Lunet cells were transfected with either a wild-type GT 1b replicon or one engineered to contain mutations resulting in reduced sensitivity to VX-950 (A), HCV-796 (B), R1479 (C), or PSI-6130 (D). The transfected cells were incubated with various HCV inhibitors for 72 h, and then the replicon luciferase activity was measured. The EC₅₀ determinations were obtained from at least three independent experiments: Con1, n = 6 for R1479, n = 8 for VX-950, n = 5 for PSI-6130, and n = 6 for HCV-796; V36M, n = 5 for R1479, n = 6 for VX-950, and n = 4 for PSI-6130; T54A, n = 4 for R1479 and VX-950 and n = 3 for PSI-6130; R155K, n = 3 for R1479 and PSI-6130 and n = 4 for VX-950; V36M+R155K, n = 5 for R1479 and n = 3 for VX-950 and PSI-6130; A156S, n = 5 for R1479 and PSI-6130 and n = 6 for VX-950; A156T, n = 4 for R1479 and n = 3 for VX-950 and PSI-6130; V36M+A156T, n = 3 for R1479, VX-950, and PSI-6130; A156V, n = 6 for R1479, n = 4 for VX-950, and n = 3 for PSI-6130; S96T, n = 6 for R1479, n = 8 for VX-950, and n = 4 for HCV-796; S96T+N142T, n = 6 for R1479, n = 7 for VX-950, and n = 4 for HCV-796; C316Y, n = 4 for R1479, n = 5 for PSI-6130, and n = 6 for HCV-796; S365T, n = 3 for R1479 and PSI-6130 and n = 5 for HCV-796; M414I, n = 4 for R1479 and n = 3 for PSI-6130 and HCV-796; and S282T, n = 6 for VX-950, n = 4 for PSI-6130, and HCV-796. The fold change of the inhibitor was determined as the EC₅₀ of the inhibitor against the mutant replicon compared to the wild-type replicon and is presented as mean ± standard error of the mean.