Genome evolution of dengue virus serotype 1 under selection by <i>Wolbachia pipientis</i> in <i>Aedes aegypti</i> mosquitoes
Duong Thi Hue Kien, Kathryn Edenborough, Daniela da Silva Gonçalves, Tran Thi Diem Thuy, Etiene Casagrande, Huynh Thi Le Duyen, Vo Thi Long, Le Thi Dui, Vu Thi Tuyet Nhu, Nguyen Thi Giang, Huynh Thi Xuan Trang, Elvina Lee, I’ah Donovan-Banfield, Huynh Thi Thuy Van, Nguyet Minh Nguyen, Nguyễn Thanh Phong, Nguyễn Văn Vĩnh Châu, Bridget Wills, Sophie Yacoub, Heather A. Flores, Cameron P. Simmons
Abstract
Abstract The introgression of antiviral strains of Wolbachia into Aedes aegypti mosquito populations is a public health intervention for the control of dengue. Plausibly, dengue virus (DENV) could evolve to bypass the antiviral effects of Wolbachia and undermine this approach. Here, we established a serial-passage system to investigate the evolution of DENV in Ae. aegypti mosquitoes infected with the wMel strain of Wolbachia. 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 wMel-infected Ae. aegypti 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 wMel-associated selection of virus populations can occur in experimental conditions. Field-based studies are needed to explore whether wMel imparts selective pressure on DENV evolution in locations where wMel is established.