Modeling the influence of temperature on the evolution of vector-virus interactions - PROJECT SUMMARY Warmer temperatures have been associated with increased virus transmission and emergence of novel pathogens and vectors in new locations. Temperature is well documented to have a significant effect on viral fitness and replication, which is particularly relevant in ectothermic vectors of enzootic viruses such as mosquitoes. Temperature also impacts numerous aspects of invertebrate biology and therefore is a critical factor influencing the transmission potential of vector populations. Studies to date which aim to model environmental effects on population level viral dynamics assume static biological systems. Given the strong effects of temperature on viral replication rates (and consequently evolutionary rates), the variability of vector species and population responses to temperature, and the documented role of interactions among viral genotype and environment in governing transmission, this assumption is flawed. This represents a clear gap in our understanding of pathogen transmission theory and a barrier to developing accurate predictive models. West Nile virus (WNV; Flavivirus, Flaviviridae) is the most prevalent arbovirus in the U.S. and the ideal candidate for modeling how temperature and viral genotype interact to influence transmission and evolution of arboviruses in dynamic vector populations. There is large variability in prevalence in mosquitoes over both fine and broad temporal and geographic scales, and this variability has been well-documented in the U.S. Variation in temperature and viral genotypes have also been documented over similar scales. We will utilize novel laboratory data to refine predictions of arbovirus transmission under various evolutionary and climate scenarios, and ultimately to create more informed predictive models that should have broader implications for vector-borne pathogens.