Spontaneous Diabetes Mellitus Associated with Persistent Bovine Viral Diarrhea (BVD) Virus Infection in Young Cattle

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Abstract
Histologic and immunohistochemical studies were carried out on four young cattle with diabetes mellitus associated with persistent bovine viral diarrhea (BVD) virus infection. Clinical findings included persistent hyperglycemia, decreased glucose tolerance, glycosuria, polydipsia, and severe emaciation. Macroscopically, multiple erosions and ulcers in the mucosa of upper and lower alimentary tracts and swollen lymph nodes were commonly observed. Erosions and ulcers in the mucosa of tongue, esophagus, and forestomach were represented histologically by necrosis of squamous epithelium with neutrophilic infiltration. In the small and large intestines, villous atrophy and suppurative cryptitis were often observed, along with diffuse infiltration of lymphocytes and macrophages and fibroplasia in the lamina propria. In the pancreas of all cattle, there was a reduction in the number of islet cells, and most of the residual islet cells had hydropic degeneration and a decreased number of secretory granules. Immunohistochemical examination confirmed that these cells were severely degranulated β-cells. In addition, many islets containing necrotic islet cells were observed. These islet cells had increased eosinophilia and shrinkage of cytoplasm, as well as pyknotic nuclei. Inflammation of the islets with mild infiltration of lymphocytes was observed in all pancreatic lobes. In addition, bovine IgG-immunoreactive cells were identified immunohistochemically in the affected pancreatic islets. The BVD virus antigen was not identified in the cytoplasm of the islet cells by immunohistochemical study, although it was identified in the epithelial cells of the small intestine. The histologic and immunohistochemical studies demonstrated that the pancreatic lesions in these animals were similar to those caused by acute insulin-dependent diabetes mellitus (IDDM) in human beings. These findings suggest that IDDM in Japanese Black cattle is an autoimmune disease induced through persistent infection by BVD virus.