Dissertation
The pathogenesis of vasculitis in sheep-associated malignant catarrhal fever in American bison
Washington State University
Doctor of Philosophy (PhD), Washington State University
08/2010
DOI:
https://doi.org/10.7273/000006184
Abstract
Sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2), a [gamma]-herpesvirus in the Macavirus genus, is a frequently fatal disease characterized by lymphoproliferation, vasculitis, and mucosal ulceration in immunocompetent American bison (Bison bison), cattle (Bos taurus), and other clinically susceptible species. Currently, the pathogenesis of disease in SA-MCF is poorly understood, and the immunophenotype of lymphocytes that infiltrate the vascular lesions of bison and cattle with SA-MCF has been only partially defined. Previous studies have demonstrated that CD8+ cells and CD4+ cells predominate within vascular infiltrates in cattle and bison, and the CD8+ cells detected in the vascular lesions of cattle and bison were assumed to be cytotoxic [alpha][beta] T lymphocytes. However, polychromatic immunophenotyping analyses in described in the first chapter showed that CD8+ /perforin+ [gamma][delta] T cells, CD4+ /perforin- [alpha][beta] T cells, and B cells infiltrate vascular lesions in the urinary bladder, kidney, and liver of six bison with experimentally-induced SA-MCF. CD8+ [alpha][beta] T cells and WC1+ [gamma][delta] T cell cells were only infrequently and inconsistently identified. This study confirmed our hypothesis that the predominant CD8+ lymphocytes infiltrating the vascular lesions of bison with SA-MCF are cytotoxic lymphocytes of the innate immune system, not CD8+ [alpha][beta] T cells. These results support the previous suggestions that MCF is fundamentally a disease of immune dysregulation. The cellular tropism of OvHV-2 in bison has not been fully defined, and the goal of the second study was to determine the cellular tropism with respect to vasculitis lesions. Transcripts of open reading frame 25 (ORF25) encoding the viral capsid protein have been detected in peripheral blood leukocytes and tissues of bison with SA-MCF. Since there is evidence of OvHV-2 DNA within lymphocytes but not within vascular structural cells, we hypothesized that perivascular lymphocytes express ORF25 protein within vascular lesions of bison. This hypothesis was refuted by the demonstration of ORF25 protein in activated fibroblasts but not lymphocytes within the vascular tunica adventitia in six bison with experimentally-induced SAMCF. These findings provide a new foundation for defining the pathogenesis of vasculitis in bison with SA-MCF.
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Details
- Title
- The pathogenesis of vasculitis in sheep-associated malignant catarrhal fever in American bison
- Creators
- Danielle Darracq Nelson
- Contributors
- J. Lindsay Oaks (Chair)Wendy C Brown (Committee Member)HONG LI (Committee Member)Guy Hughes Palmer (Committee Member) - Washington State University, Paul G. Allen School for Global Animal Health
- Awarding Institution
- Washington State University
- Academic Unit
- College of Veterinary Medicine
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 85
- Identifiers
- 99901055127501842
- Language
- English
- Resource Type
- Dissertation