title: The impact of transgenic mosquitoes on dengue virulence to humans and mosquitoes.
abstract: Dengue is a major public health concern in the tropics and subtropics. Innovative transgenic strategies to render Aedes aegypti mosquitoes, the primary vector of dengue, incompetent for dengue transmission are under development. We modeled the evolutionary impact of different transgenic mosquito strategies on dengue-induced mortality, that is, dengue virulence, to both humans and mosquitoes. This model incorporates various evolutionary trade-offs in dengue virus epidemiological traits, for example, a trade-off between dengue transmission rate and its virulence to humans. Our results indicate that strategies that block transmission or reduce mosquito biting impose selection on dengue virulence in humans. This selection can be for either higher or lower virulence, depending on the interaction between the effect of the transgene and the trade-offs in epidemiological traits, highlighting the need for detailed quantitative data to understand more fully the impact of mosquito transgenesis on dengue virulence. Dengue virulence in mosquitoes can be selected on by transgenic strategies of blocking transmission, decreased mosquito biting, increased mosquito background mortality, and increased mosquito infection-induced mortality. Our results suggest that dengue control strategies that raise mosquito background mortality or mosquito infection-induced mortality pose less risk of causing increased virulence to humans than strategies that block transmission or reduce mosquito biting.
authors.affiliation: Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA. medlock@clemson.edu
authors.forename: Jan
authors.initials: J
authors.lastname: Medlock
authors.forename: Paula M
authors.initials: PM
authors.lastname: Luz
authors.forename: Claudio J
authors.initials: CJ
authors.lastname: Struchiner
authors.forename: Alison P
authors.initials: AP
authors.lastname: Galvani
mesh_terms: D000330:Aedes / Q000235:genetics* / Q000821:virology; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000821:virology; D003715:Dengue / Q000517:prevention & control* / Q000635:transmission; D003716:Dengue Virus / Q000472:pathogenicity*; D005247:Feeding Behavior; D006801:Humans; D007303:Insect Vectors / Q000235:genetics / Q000821:virology; D008957:Models, Genetic; D012641:Selection, Genetic; D014774:Virulence