FIG. 4.

Serial passage of MARLS (top panels) and C₂₂⁹ (bottom panels) in the absence or presence of FU or AZC. FMDV MARLS and C₂₂⁹ are described in Materials and Methods. MARLS has a 1,300-fold-higher relative fitness than C₂₂⁹ (19; Sierra and Escarmís, unpublished). The experimental design is identical to that described in the legend to Fig. 2. Empty circles correspond to serial passages of undiluted virus in the absence of a mutagen. Filled circles correspond to passages of undiluted virus, and squares correspond to passages in which the virus was diluted 10-fold prior to infection, irrespective of the virus titer obtained. Preextinction populations are indicated by arrows. Loss of infectivity was ascertained by absence of infectivity and RT-PCR-amplifiable material after three blind passages, as detailed in Materials and Methods and the legend to Fig. 2.