(A) Representation of drug-resistant viral amplification when a non-dominant drug target is inhibited (top) but its inhibition by drug-susceptible variants when a dominant drug target, such as an oligomeric structure, is inhibited (bottom). See text for discussion. (B–K) Tnfr1+/+ (B, C) or Tnfr1−/− (d-k) PVR-expressing mice were infected with 1 × 107 PFU Mahoney type 1 poliovirus by intramuscular inoculation and treated with 76 mg/kg/day guanidine (B–E, green symbols) or 10 mg/kg/day V-073 (1-[(2-chloro-4-methoxyphenoxy)methyl]-4-[(2,6-dichlorophenoxy)methyl]benzene) (F–K, orange symbols). Inoculated muscles were harvested at times indicated. Total viral yields (PFU/mg tissue) in muscle samples of mice treated with guanidine (B, D), V-073 (F, H, J) or vehicles (black) are shown. Fold changes in the frequency of drug-resistant variants in mice treated with guanidine (C, E) or V-073 (G, I, K) are shown. Fold change calculated by dividing sample value by mean value of control mice. p-values: 0.02 (B), 0.003 (C), 0.0002 (D) 0.02 (E), and 0.01 (F, H, J combined).