: Arthropod-borne viral disease have re-remerged as major health problems in most tropical countries. The incidence of dengue fever has increased greatly over the pat 20 years, including its hemorrhagic form with associated human fatalities. Dengue is a treat to >2.5 billion people, with a annual incidence estimated at 50-100 million and several hundred thousand cases of DHF with approximately 24,000 death per year. Dengue control efforts have been limited by the lack of progress in vaccine development, development of insecticide resistance in mosquito vectors, and the general decline in organized mosquito control efforts. The objective of this proposal is to identify, isolate and characterize genetic factors associated with mosquito vector competence for dengue virus, with a long-term goal of using this information to develop novel dengue disease control strategies aimed toward disrupting the pathogen life cycle. The proposed objectives are based on the general hypothesis that a core suite of genes that are differentially regulated in response to exposure to different dengue serotypes can be identified among both laboratory strains and geographic field collections of the mosquito, Aedes aegypti. The research plan employs one of the first products of the Ae. aegypti genome project, microplate-arrayed and partially sequenced cDNAs, as a gateway into the eventual complete elucidation of these gene relationships and their phenotypic outcome. The outlined experiments represent the application of first generation cDNA micro-arrays for high-throughput expression analysis in Ae. aegypti following a dengue virus challenge, detailed analysis of differentially expressed genes, and the rapid transition of information gained from laboratory studies into field studies. Field studies will be conducted in Trinidad and Haiti, as they represent dengue endemic countries with organized versus limited vector control programs, respectively.
The specific aims of this project are: 1) characterize differential gene expression patterns in Ae. aegypti following a dengue-infected blood meal; 2) conduct functional analysis od candidate dengue vector competence genes; and, 3) investigate the impact of selected biotic and abiotic factors on dengue transmission in endemic areas, including key candidate dengue vector competence genes identified by micro-array analysis.
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