DESCRIPTION: (provided by the applicant): West Nile virus (WNV) has emerged in recent years in temperate regions of Europe, Eastern Europe, the Middle East, and North America, where it presents a threat to human, equine and avian health. The virus was first identified in the Western Hemisphere in 1999 when humans, mosquitoes, birds and horses in a limited area near New York City were found infected. In year 2000, WNV positive birds were identified from a wider geographic area of the United States including 12 states in the northeast, from New Hampshire to North Carolina. The emergence and adaptation of arboviral diseases involve complex interactions between intrinsic (virus, vertebrate host and arthropod vector) and extrinsic (environmental conditions, host population indices, etc.) factors affecting the virus transmission cycle. The introduction of WNV into naive populations presents a unique and historic opportunity to prospectively study the emergence and adaptation of WNV. The proposed research will examine how the interrelationships of the vertebrate and invertebrate hosts with the virus affect virus and host populations over time. Research will address three intrinsic components of the virus transmission cycle: 1. Vertebrate: Studies will analyze the morbidity, viremia, humoral immune response, and genetics of WNV infected birds and will examine changes in these factors over the five-year study. 2. Vector Studies will analyze spatially and temporally, disparate populations of Culex pipiens for vector competence, genetic markers, and effects on viral genetic diversity and fitness. 3. Virus: Studies will analyze how the virus transmission cycle impacts viral genetics and fitness and the ability of the virus to adapt to the temperate environment of northeastern USA. The cycles to be evaluated include alternating bird-mosquito passages, sequential passages between birds, sequential passages between mosquitoes, and host switching from bird-mosquito to mammal-mosquito cycle.