Immunohistochemical Detection of Intralesional Antigens of Ovine Gammaherpesvirus-2 in Cattle with Sheep-associated Malignant Catarrhal Fever

Sheep-associated malignant catarrhal fever (SA-MCF) is a severe lymphoproliferative disease of ruminants caused by ovine gammaherpesvirus-2 (OvHV-2). Since the initial identification of SA-MCF there has been extensive research related to the pathogenesis of OvHV-2, based primarily on serological and molecular assays associated with typical histopathological findings. The monoclonal antibody (MAb-15A) binds to a common epitope in MCF viruses and is used frequently in serological investigations. However, the utilization of this antibody to detect antigens of OvHV-2 in tissues has not been examined. Accordingly, this study standardized an immunohistochemical assay using MAb-15A to identify antigens of OvHV-2 in tissues of cattle (n = 5) with SA-MCF. All animals developed acute neurological signs, without ocular and nasal manifestations, and had nucleic acids of OvHV-2 in brain tissue detected by polymerase chain reaction. The principal histopathological findings were lymphocytic nephritis (n = 5), widespread arterial proliferation and vasculitis (n = 5), lymphocytic portal hepatitis (n = 3), non-suppurative meningoencephalitis (n = 2) and atrophic enteritis with cryptal necrosis and dilation (n = 2). Intralesional intracytoplasmic antigens of OvHV-2 were identified within multiple epithelial cells of the kidneys of all animals, the intestines of animals with and without atrophic enteritis, and within epithelial cells of bile ducts in animals with lymphocytic hepatitis. Additionally, there was positive intracytoplasmic immunoreactivity within histiocytes and lymphocytes in several tissues. These findings suggest that the MAb-15A detects antigens of OvHV-2 within epithelial cells and leucocytes in several organs. Moreover, this assay would contribute significantly towards understanding of the pathogenesis of SA-MCF and may be used for retrospective studies. Additionally, angiopathy in SA-MCF may be a progressive lesion, which may terminate in luminal occlusion and probably occurs irrespectively of the eye and head form of MCF.