Invited by Suzanne Faure-Dupuy, Alberto De la Iglesia and Hugo Barreto, part of the Post-doc seminar series.

Viral pathogens transmitted by mosquitoes represent a growing threat to human health, due to global warming and globalization. For example, Aedes aegypti (Ae. aegypti) mosquitoes are the main vectors of dengue viruses (DENV) that infect 400 million people annually. Previous studies showed that the ability of a given mosquito population to acquire and transmit a given virus is highly variable. The mechanisms underlying natural variation in susceptibility to viral infection between different mosquito populations remain mostly unknown. To explore this, we combined single-cell transcriptomics and metabolomics on Ae. aegypti populations showing contrasted infection phenotypes after DENV exposure.

We identified Ae. aegypti mosquito populations, recently collected in the field, that are either resistant or susceptible to infection with DENV. When a mosquito bites a virus-infected human, the bloodmeal containing viral particles enters the mosquito’s digestive tract and is digested in the midgut, which is the entry gate for viruses into the mosquito’s body. Subsequently, the virus infects the fat body, the main immune and metabolic organ. We analyzed infection dynamics in those two mosquito organs and subjected them to single-cell RNA sequencing and tissue metabolomics analysis, in both resistant and susceptible Ae. aegypti populations. We described the metabolic functions of different cell subpopulations of the mosquito midgut and fat body upon DENV infection. We revealed metabolic pathways and gene expression patterns associated with susceptibility to virus infection at the organ and cellular levels. Results obtained from this study identify mosquito factors underlying natural variation to DENV infection and could lead to innovative tools for preventing arbovirus transmission.