Modulação da resistência de mosquitos Aedes Aegypti ao vírus da dengue pela rotenona, um inibidor do complexo I da cadeia respiratória

Abstract

Dengue virus, caused by the dengue virus (DENV), is one of the most important infectious diseases in the world. At the moment, there are no vaccines or effective treatments for DENV, which reinforces the need to combat the transmission of DENV by mosquito vectors mainly of the species Aedes aegypti. Data from our group suggest that, between the same population, there may be resistant (not infected) and susceptible (infected) mosquitoes when fed with the same blood infected with DENV. To try to understand the biological basis of the difference between resistant mosquitoes and susceptible mosquitoes, analyzes of the transcriptome of each group were carried out. We observed several differentially enriched pathways between resistant and susceptible mosquitoes, and oxidative phosphorylation being the path that stood out the most. This pathway consists of five complexes, and complex I being the most differentially expressed among susceptible and resistant mosquitoes. Based on these previous results, the objective of dissertation was to study the role of complex I of the oxidative phosphorylation pathway in the resistance / susceptibility of Aedes aegypti mosquitoes to DENV. To this end, we decided to chemically block complex I with the drug rotenone, which blocks the release of electrons from complex I to complex III and to analyze the resistance / susceptibility effect to DENV in adult mosquitoes. We performed experiments to standardize the dose of rotenone to be administered orally, and we observed that the concentrations 0.01 mM and 0.001 mM did not significantly affect the survival of mosquitoes. To assess the effect of complex I block, we compared the infection rate and viral load of mosquitoes fed with blood containing these concentrations of rotenone and DENV1. We observed that mosquitoes fed with blood containing rotenone had a lower infection rate in the midgut and carcass, suggesting that inhibition of complex I confers resistance to DENV1 infection. This study functionally validates a prediction of our wild mosquito transcriptome data and opens the way for understanding the molecular basis of mosquitoes' natural resistance to the Dengue virus.