Bovine leukemia virus (BLV) is a deltaretrovirus which infects more than 40% of the United States cattle population and more than 85% of U.S dairy herds. Upon infection of a susceptible host, BLV reverse transcribes its viral RNA genome into a DNA provirus that integrates into the cellular DNA of the host, resulting in a lifelong infection. Clinical outcomes of BLV infection are the development of lymphocytosis in more than 30% of infected cattle and the development of lymphoma in less than 10%. Furthermore, BLV infected cattle have been shown to be immunocompromised, to produce less milk, and to have shortened lifespans when compared to their uninfected herd mates. Collectively, these impacts warrant the consideration of disease eradication from the U.S. cattle population. In fact, eradication has already been achieved in more than 21 countries, predominately within the European Union.One objective of our BLV research team has been to develop BLV management solutions that are both practical and economically feasible. The goal of this dissertation was to contribute to these efforts by providing a greater understanding of the routes through which BLV can be transmitted, by describing how BLV progresses over time to disease states associated with increased infection potential, and by understanding how newly available diagnostics can best be utilized to detect BLV infections.To contribute to the identification of BLV transmission routes, a statistical model was built to examine the association between herd management practices and the BLV incidence rate among Michigan dairy herds. This analysis estimated the marginal incidence rate in Michigan dairy herds to be 2.11 infections per 100 cow-months at risk. Herd management practices positively associated with herd-level rate of infection were herd prevalence, the frequency of needle reuse, housing post-parturient cows separately, and increased milking frequency. The use of sand bedding appeared to have protective effects and was negatively associated with the incidence rate. To describe how BLV progresses over time, longitudinal observations on proviral load, lymphocyte counts, and ELISA test results collected during an intervention field trial were analyzed. The results from this analysis indicated that negligible increases in lymphocytes and small increases of approximately 3,000 proviral copies per 100,000 cells occurred over a six-month interval. Additionally, infected cattle with low proviral loads and normal lymphocyte counts were the most likely to experience changes in ELISA status that may result in ELISA false-negatives. To determine our ability to detect BLV infections and to examine the role early infection plays in long-term disease progression, fifteen steers were experimentally infected with BLV and followed for 147 days. This study found that new infections are detected by PCR on average 24 days post infection prior to detection by ELISA at 36 days post infection. Furthermore, the observations on early viral kinetics suggest BLV proviral load and lymphocyte count levels may be established soon after initial infection. Overall, the results of this dissertation contribute to ongoing BLV control efforts by identifying new potential routes of transmission that can be explored in future intervention trials, finding that the development of PVL and LC may not be the result of gradual disease progression but may be established shortly after infection, and determining the relationships among the various BLV diagnostic tests.
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