Mosquito-virus matchmaking: Elucidating the biological basis of compatibility between viruses and mosquitoes

Half of the world's population is at risk for mosquito-borne diseases. Yet, less than 3% of the mosquito species on earth can transmit pathogens to humans. Even within a species that specializes in biting humans and is the major vector for dengue virus (Aedes aegypti), mosquito populations on the globe transmit DENV with a wide range of efficiencies. Thus, some virus-mosquito pairs "match" with each other, and enable viral transmission, while others don't. Understanding the biological processes that determine virus-mosquito compatibility is a longstanding question that has not yet been addressed, mostly owing to a lack of appropriate methods. Here, I propose to leverage advances in single-cell technology, gene editing and computational tools to understand the basis of virus-mosquito matchmaking. I will address three related challenges: 1 - Obtain single-cell transcriptional and epigenetic atlases for key organs of "matched" or "unmatched" virus-mosquito pairs. To be retransmitted, a virus needs to infect and transit through key organs in a mosquito's body. Unknown factors that interfere with viral infection and impact further transmission exist in mosquito cells. They will be detected with single-cell technologies. 2 - Identify the key drivers of virus-mosquito matchmaking. Using cutting-edge single-cell data analysis methods, I will determine which genetic or epigenetic processes are associated with "matched" and "unmatched" virus-mosquito pairs. 3- Reprogram virus-mosquito matchmaking using genome editing. With key factors of matchmaking identified, I will genetically interfere with their function and determine whether virus-mosquito pairs can artificially be "matched" or "unmatched". ITSaMATCH will combine new technologies to unravel the basis for virus-mosquito matchmaking. The project has the potential to substantially advance our understanding of virus-mosquito interactions and inform novel disease control strategies.