Suppression of Drug Resistance in Dengue Virus

Mateo, Roberto; Nagamine, Claude M.; Kirkegaard, Karla

During 4 days of viral growth in dengue virus-infected mice, selection for ST-148-resistant viruses was not observed, even though, under the same circumstances, resistance to the nucleoside inhibitor MK-0608 increased significantly (Fig. 5C ). Although it is possible that mutations leading to ST-148 resistance are not frequently generated or that ST-148-resistant viruses show reduced fitness in the mouse, these hypotheses seem unlikely, because generation of the C-S34L mutant virus requires only a single nucleotide change from the wild-type virus and it was readily selected at a low MOI in cultured cells (12) . Instead, we argue that the mechanism of suppression of ST-148-resistant virus in the mouse is the same as that observed in tissue culture. The continued suppression of drug resistance over 4 days of infection could indicate that viral spread is local, such as might occur in the lymph nodes or spleen.