Exploring the ecology of Orthobunyaviruses in Virginia and their pathogenesis in murine and poultry models

Cache Valley virus (CVV) is a vector-borne, negative-sense RNA virus, in the genus orthobunyavirus. Cache Valley Virus is a widespread pathogen in North America, and since its first isolation in 1956, has been associated with multiple epizootics of CVV in ruminants, leading to spontaneous abortions and congenital malformations. As such, CVV is a virus of high economic relevance, but little is known about fundamental aspects of its biology. To address this gap of knowledge, I conducted a series of studies to better understand the pathogenesis and ecology of CVV. This work is divided into two facets; the first is the development of animal models to assess the pathogenesis of CVV in various host species, and the second is vector surveillance to better understand the ecology of orthobunyaviruses within the Commonwealth of Virginia. In the first two chapters, I address the lack of small animal models to study CVV. First, I developed a murine model and an in utero model that mimic the natural progression of disease observed in CVV infection. In the second chapter, I study the growth kinetics of CVV in avian cell lines and in commercial poultry species. In the last chapter, I explore the distribution and diversity of mosquitoes and arthropod-borne viruses in Virginia. Overall, these studies provide insight into CVV pathogenesis and in utero transmission, the role of domestic poultry in the maintenance and amplification of CVV, and lastly, evidence of mosquito species range expansion, and high viral diversity across the Commonwealth of Virginia.