The development of a Murine model for epizootic hemorrhagic disease virus

Hemorrhagic Disease (HD) is an arthropod borne disease caused by two genetically related but distinct groups of viruses, the bluetongue (BTV) and epizootic hemorrhagic disease viruses (EHDV). HD has been responsible for... [ view full abstract ]

Hemorrhagic Disease (HD) is an arthropod borne disease caused by two genetically related but distinct groups of viruses, the bluetongue (BTV) and epizootic hemorrhagic disease viruses (EHDV). HD has been responsible for numerous morbidity and mortality events in white-tailed deer (WTD; Odocoileus virginianus) and other wild ruminants throughout the United States, and EHDV has recently been recognized as an emerging disease (~2006) in domestic cattle. In order to better study viral-host-vector interactions, there is a need for experimental animal models for both BTV and EHDV that are reliable and reproducible. Most animal experiments with EHDV have utilized large ruminants such as white-tailed deer, sheep and cattle. Practical justifications for use of a small animal model over traditional large animal studies include, but are not limited to, less variable outcomes in clinical disease, reduced cost and, in the case of deer, improved animal availability. The IFN-α/β knockout mouse, IFNAR (-/-), has created opportunities for more in-depth study of viral pathogens and has been utilized in BTV pathogenesis studies. The proposed study aims to evaluate three laboratory mouse strains: IFNAR (-/-), Toll-like receptor 3 deficient (TLR-3(-/-)), and severe combined immune deficient (SCID), related to their ability to produce a viremia and detectable antibody response in response to EHDV infection. Preliminary data indicates that IFNAR (-/-) mice infected with EHDV reach peak viremia on day 3 (spleen CT-value: 25.7, blood CT-value: 29.2). The most common tissue positive for virus isolation was spleen (8/10), followed by the liver (7/10), and lung (6/10). Blood was positive for virus on day 3 (2/2) and day 5 (1/2). CT values for virus isolation positive blood samples were 29.29 and 29.71 on day 3 and 28.7 on day 5. The viremia observed in IFNAR (-/-) mice suggests they may be a model to experimentally investigate EHDV vector/host relationships.