FIG. 4.
Two distinct resistance profiles are found in the context of virus infection. Clonal, adapted MeV-Edm-1* (adapMeV) shows intermediate-level resistance, while all other replicon-confirmed L mutations mediate high-level (>135-fold) resistance. For the latter, individual L mutations were rebuilt in a cDNA copy of the MeV genome and recombinant MeV was recovered. Vero cells were then infected with these variants or unmodified recMeV-Edm for comparison in the presence of different AS-136A concentrations or vehicle control (concentration [C] = 0) at an MOI of 0.1. Cell-associated viral particles were harvested 30 h postinfection and subjected to TCID50 titration. Averages from three independent experiments ± standard deviations are shown. Asterisks represent P values derived from t test analysis for adapMeV-Edm L(R1233Q) P(M502V) (**, P < 0.01; *, P < 0.05).