MetAeAvIm · The Role of the Metabolism in Mosquito Immunity against Dengue virus in Aedes aegypti

Mosquito-borne diseases remain among the most prevalent diseases in the world with. At present, more than half of the world population lives in areas where mosquito vectors are present. Vector control is one of the cornerstones of arbovirus control. However, insecticide-resistant population are emerging demanding new tools of vector control to be developed. It is known that mosquito immunity can be modulated by its physiological state and nutritional status. However, we still lack an integrated view of how immune mechanisms and metabolic pathways interact to control viruses at different stages of infection. In order to obtain a more detailed understanding of the gene expression profile associated with immunity to Dengue virus (DENV), we performed a genome-wide analysis of the transcriptome of susceptible and resistant individuals from the same population of mosquitoes. Metabolic pathways represented the majority of the differentially expressed gene sets identified by our analysis, suggesting that differences in metabolism determine DENV resistance. These results support the hypothesis that mosquito metabolism plays a key role in controlling mosquito susceptibility to viral infections. In this project, we will characterize the metabolism of mosquitoes and characterize pathways and genes that are determinants for DENV resistance. We will study the metabolism of A. aegypti, comparing susceptible and resistant mosquitoes, measuring specific metabolic outputs and also performing unbiased high-throughput metabolomic studies. In parallel, we will perform reverse genetic screenings to validate whether metabolic pathways and biological processes identified in our transcriptomic analysis have a role in vector competence to DENV. Finally, we will apply the CRISPR/Cas9 technology and classical transgenesis to target genes and pathways that affect vector competence in mosquitoes. Together, this project will allow for a deeper mechanistic study of mosquito antiviral immunity.