Dengue virus occurs as 4 serotypes that are biologically transmitted between humans principally by Aedes aegypti mosquitoes. Dengue and the more severe forms, dengue hemorrhagic fever and dengue shock syndrome, remain a global threat to >2.5 billion people. Collectively, these result in significant annual morbidity an mortality that is likely underestimated. No effective licensed vaccines or drug therapies are currently available for preventing dengue transmission. Presently, mosquito control remains the only prevention option, but this can be compromised by several factors including emergence of insecticide resistance in the mosquito and political/economic issues impacting vector control in disease endemic countries. The long-term objectives of this research are to identify, isolate and characterize biotic and abiotic factors associated with Ae. aegypti vector competence for dengue virus (DENV), and to use this information to develop novel dengue disease control strategies aimed toward disrupting the pathogen life cycle. It seeks to integrate studies of vector population biology and ecological genetics/genomics with contemporary laboratory- based molecular analyses to uncover the complex networks of genetic interactions that drive the observed phenotypic plasticity in Ae. aegypti populations. A systems biology approach is used to identify those interactions most likely to influence DENV transmission. The central hypothesis is that genic and environmental factors intersect to determine spatio-temporal variation in DENV vector competence among Ae. aegypti populations, and that this information once available can subsequently be leveraged to enhance existing conventional control programs or to provide a foundation for a next generation of targeted and effective DENV control technologies. Project specific aims include: 1) Examine seasonal effects on select adult phenotypes including DENV vector competence in a dengue endemic region; and 2) Investigate gene by environment effects on DENV vector competence under lab vs. field conditions.
Dengue is a significant reemerging global disease with no effective licensed vaccines or drug therapies available. Control of the mosquito vector remains the only disease prevention option. This research proposal seeks to uncover biotic and abiotic factors determining the ability of the mosquito to transmit dengue virus with a goal of leveraging this information to enhance existing dengue control strategies or to provide a foundation to develop novel genetic control strategies that target the mosquito.
