The Role of Long Distance Movement and Genetic Adaptation on the Evolution of West Nile virus in the New World

West Nile virus (WNV) is an emerging arbovirus that is maintained in an epizooitic cycle involving birds and mosquitoes. After a long history of circulation in the Old World, WNV was introduced into the US and identified in the New York Metropolitan Area during the summer of 1999. While the initial outbreaks were restricted to the northeastern USA, the geographic range of WNV expanded rapidly south reaching Florida and the Caribbean by 2001, and west to California by 2003. The accelerated rate and distinct pattern of expansion suggested that migratory birds played a role in the dissemination of WNV throughout the New World. In this study, the general patterns of WNV circulation were defined in the Americas revealing correlation between the movement of WNV and the migration of terrestrial birds. To our knowledge, this is the first time phylogeographic methods have been used to correlate pathogen and terrestrial bird migration in the New World. The major sources of WNV migration events were also identified to determine the optimal locations for targeted surveillance efforts (New York, Illinois and Texas). To investigate the effectiveness of monitoring WNV evolution in these locations, recent isolates from Texas were analyzed using Next Generation Sequencing and phylogeny. The results of this analysis demonstrated that WNV sequences collected in Texas could be used to identify genetic selection occurring throughout the country. However, sequencing data could not be used to predict virulence as there was no relationship between intra-host variation and phenotype. Finally, the relationship between WNV circulating in North and South America was considered. The results of this analysis confirmed that WNV circulating in South America was introduced from North America prior to 2001. Together the results of this dissertation demonstrate the power of using sequencing and phylogeny to inform public health strategies.