Final Report Summary - VIVARNASILENCING (Antiviral Defense in the Vector Mosquito Aedes aegypti: induction and suppression of RNA silencing pathways) Mosquitoes transmit viruses like Zika, Chikungunya, and Dengue, which are responsible for debilitating disease and worldwide epidemics. For example, dengue virus causes >100 million infections per year. These viruses are transmitted by two vector mosquito species, Aedes aegypti and Aedes albopictus. Complex interactions between virus and mosquito determine how efficient virus transmission occurs by these mosquitoes. Crucial in this interplay is the small RNA-based immune response of the mosquito, which recognizes and degrades viral RNA. In this ERC Consolidator project, we have analyzed the biogenesis, mechanisms and functions of small RNA-mediated antiviral defense in the mosquito Aedes aegypti. We have focused on a novel class of viral RNAs, called PIWI-interacting RNAs, thus far mostly studied for its function in suppressing mobile elements in the genomes of model organisms such as fruit flies. We find that the piRNA pathway processes viral RNA of a range of different viruses and we identified the mechanism by which this pathway recognizes viral RNA. In addition, we found that the piRNA pathway plays important functions in the regulation of cellular genes. We propose that PIWI proteins in Aedes aegypti are functionally specialized to exert multiple functions, including antiviral defense and gene regulation.
