Estudo do papel do complexo i da cadeia respiratória mitocondrial na resistência de mosquitos Aedes Aegypti

Abstract

The Dengue virus (DENV), caused by dengue fever, is one of the most significant infectious diseases in the world. Currently, there are vaccines available, but Brazil is experiencing its highest season of disease infections in 2024, emphasizing the need to combat DENV transmission carried by vector mosquitoes, mainly of the Aedes aegypti species. Data from our group suggest that within the same population, there may be mosquitoes that are resistant (not infected) and susceptible (infected) when fed with the same blood infected with DENV. To try to understand the biological basis of the difference between resistant and susceptible mosquitoes, analyses of the transcriptome of each group were performed. We observed several differentially enriched biological pathways between resistant and susceptible mosquitoes, with the oxidative phosphorylation (OP) pathway standing out the most. Leading Edge Analysis (LEA) identified that components of Complex I (CI) of OP were overrepresented. Based on these previous results, the aim of this thesis was to study the role of Complex I in the resistance/susceptibility of Aedes aegypti mosquitoes to DENV. In this work, we observed that oxidative phosphorylation genes have a significant increase in their expression in response to blood feeding, which is accompanied by increased respiration in the intestine during digestion. Furthermore, changes in mitochondrial morphology were observed after blood feeding. Using chemical inhibitors, we show that complex I is responsible for the majority of respiration in the intestine during the blood feeding response. Using Complex I inhibitors, we observed a significant reduction in the rate of intestinal DENV infection. Similarly, silencing of two genes encoding complex I supernumerary chains (ASHI and B18) led to a decrease in DENV infection. These results suggest that cellular respiration and, more specifically, the activity of Complex I oxidative phosphorylation, are essential to determine the success of DENV infection in the mosquito intestine. Our study functionally validates a prediction from our wild mosquito transcriptome data and suggests that cellular respiration rate is one of the key parameters determining the natural resistance of mosquitoes to dengue virus.