TY - JOUR T1 - Insulin potentiates JAK/STAT signaling to broadly inhibit flavivirus replication in insect vectors JF - bioRxiv DO - 10.1101/701714 SP - 701714 AU - Laura R.H. Ahlers AU - Chasity E. Trammell AU - Grace F. Carrell AU - Sophie Mackinnon AU - Brandi K. Torrevillas AU - Clement Y. Chow AU - Shirley Luckhart AU - Alan G. Goodman Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/07/13/701714.abstract N2 - The World Health Organization estimates that over half of the world’s population is at risk for vector-borne diseases, such as those caused by arboviral infection. Because many arboviruses are mosquito-borne, investigation of the insect immune response will help identify targets that could reduce the spread of these viruses by the mosquito. In this study, we used a genetic screening approach to identify insulin-like receptor as a novel component of the immune response to arboviral infection. We determined that vertebrate insulin reduces West Nile virus (WNV) replication in Drosophila melanogaster as well as WNV, Zika, and dengue virus titers in mosquito cells. Mechanistically, we showed that insulin signaling activates the JAK/STAT, but not RNAi, pathway to control infection. Finally, we validated that insulin priming of adult female Culex mosquitoes through a blood meal reduces WNV infection, demonstrating an essential role for insulin signaling in insect antiviral responses to emerging human pathogens. ER -