Genome evolution of dengue virus serotype 1 under selection by in mosquitoes.

The introgression of antiviral strains of into mosquito populations is a public health intervention for the control of dengue. Plausibly, dengue virus (DENV) could evolve to bypass the antiviral effects of and undermine this approach. Here, we established a serial-passage system to investigate the evolution of DENV in mosquitoes infected with the Mel strain of . Using this system, we report on virus genetic outcomes after twenty passages of serotype 1 of DENV (DENV-1). An amino acid substitution, E203K, in the DENV-1 envelope protein was more frequently detected in the consensus sequence of virus populations passaged in Mel-infected than wild-type counterparts. Positive selection at residue 203 was reproducible; it occurred in passaged virus populations from independent DENV-1-infected patients and also in a second, independent experimental system. In wild-type mosquitoes and human cells, the 203K variant was rapidly replaced by the progenitor sequence. These findings provide proof of concept that Mel-associated selection of virus populations can occur in experimental conditions. Field-based studies are needed to explore whether Mel imparts selective pressure on DENV evolution in locations where Mel is established.