Drug resistance profiles of plaque-purified VACV-WR (A), CPXV-BR (B), and CML1 (C) KAY-2-41r clones and of viruses with thymidine kinase deletions (D). (A to C) Three clones of each WT and drug-resistant virus were used for plaque reduction assays, and at least three to four independent experiments were performed for each compound tested. The data are presented as a dot plot of the EC50s of the KAY-2-41r clones (filled symbols) versus the EC50s of the WT parent clones (empty symbols). On top of each graph are shown the fold changes in EC50s, which were calculated as the ratio of the mean EC50s of the KAY-2-41r clones divided by the mean EC50s of the WT clones. Results are presented as means ± standard deviations. The statistical significance of the differences in drug sensitivity of the resistant viruses compared to that of the WT is indicated as follows: *, P < 0.05; ***, P < 0.001; ****, P < 0.0001. (D) Plaque reduction assays were done with each of the three KAY-2-41r strains, two VACV strains with TK deletions, and their corresponding WT viruses in three independent experiments. Results are plotted on a linear scale as the log10 of the ratios of the EC50s, and standard deviations are given. Resistance was observed with a ratio of >2 (log 0.3), and hypersensitivity was observed with a ratio of <0.5 (log −0.3).