Emergence of an infectious disease can follow the invasion of a pathogen into a naive host population in a non-endemic area. Successful introduction and establishment are often associated with changes in host density and behavior, or with changes in pathogen virulence, and may hinge on anthropogenically-determined environmental factors. Urban areas, in particular, are disturbed ecosystems, where humans, potential disease vectors and adapted wildlife coexist in very high densities, providing opportunities for rapid spread and major impacts of introduced species. Since its introduction in 1999, West Nile virus (WNV) has emerged as a major pathogen in the continental U.S., impacting wildlife, domestic animals, and humans. The rapid spread of WNV across the U.S can be studied to elucidate processes underlying biological invasion of an exotic pathogen in real-time, as well as the virus' impact on public health and wildlife conservation. The 2002 outbreak of WNV in urban areas of the north-central U.S. can contribute to the understanding of anthropogenic factors associated with the emergence of an infectious disease. The local-scale ecological processes that result in WNV emergence, spread and persistence in urban environments will be studied in the greater metropolitan areas of Chicago, Illinois. Of particular notice are historical comparative data on an outbreak associated with a related, enzootic arbovirus, St. Louis encephalitis (SLE) virus, focused in the same geographic region in 1975, which indicates some persistent risk factors and repeated manifestation of disease in specific sites. Intellectual Merit: The underlying hypothesis is that three specific environmental conditions predispose these (and other) urban areas for arboviral invasion and establishment, namely: (1) presence of storm- and waste-water catchment, channeling, and processing systems which create productive mosquito habitat; (2) establishment and maintenance of urban "green spaces" which provide roosting and nesting habitat conducive for virus susceptible bird populations and other wildlife; and (3) the phenomenon of urban "heat islands" that elevate ambient temperature and accelerate the extrinsic incubation period of West Nile virus in mosquitoes. A spatially structured simulation model and risk maps of WNV transmission will be developed based on: (1) determination of the demographic and environmental risk factors for WNV and SLE in birds, mosquitoes and humans; (2) comparison of the reservoir capacity and differential effects of WNV on various bird species; and (3) anthropogenic features of the urban environment that support Culex mosquito production, mosquito-bird transmission and virus amplification. The dynamics of viral transmission over space and time using molecular evolutionary and phylogeographic techniques will also be evaluated and incorporated into the model. This integration of a complex array of information from existing databases and field investigations with GIS-based phylogenic and population modeling methodologies will result in: (i) identification of the critical features for viral transmission, amplification, and diversification; (ii) predictions about when and where future outbreaks of WNV are likely to occur; (iii) evaluation of the efficacy that different control strategies might have in preventing new outbreaks, and (iv) uncovering of fundamental principles associated with the emergence and invasion of arboviruses. Broader Impacts: The proposed project is a joint effort of ecologists, entomologists, epidemiologists, geographers, ornithologists, virologists and wildlife biologists from academia, federal agencies, state public health departments and conservation groups in an urban setting. Beyond the scientific outcomes listed above, this project will allow for simultaneous consideration of public health and conservation interests. While the future activity of WNV is still to unfold, based on its history in New York and in the Old World, and on temporal activity patterns of related arboviruses, it appears likely that enzootic activity will continue with occasional epizootics/epidemics. The investigators and their collaborators have vast experience in collaborations, training and communications with the public, conservation groups and public health agencies. The urban setting will provide ample opportunities for public involvement and training opportunities for students, researchers, public health professionals and conservation groups.