Experimental infection of mice with noncytopathic bovine viral diarrhea virus 2 increases the number of megakaryocytes in bone marrow.

BACKGROUND: Bovine viral diarrhea virus (BVDV) causes significant economic losses worldwide in the cattle industry through decrease in productive performance and immunosuppression of animals in herds. Recent studies conducted by our group showed that mice can be infected with BVDV-1 by the oral route. The purpose of this study was to assess the clinical signs, hematological changes, histopathological lesions in lymphoid tissues, and the distribution of the viral antigen after oral inoculation with a Korean noncytopathic (ncp) BVDV-2 field isolate in mice. METHODS: Mice were orally administered a low or high dose of BVDV-2; blood and tissue samples were collected on days 2, 5, and 9 postinfection (pi). We monitored clinical signs, hematological changes, histopathological lesions, and tissue distribution of a viral antigen by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) and then compared these parameters with those in ncp BVDV-1 infections. RESULTS: None of the infected mice developed any clinical signs of the illness. Significant thrombocytopenia was found in both low- and high-dose-inoculated mice on day 2 pi. Leukopenia was apparent only in low-dose-inoculated mice on day 2 pi, whereas lymphopenia was not observed in any ncp BVDV-2-infected animal. Viral RNA was found in the spleen in of low- and high-dose-inoculated mice by RT-PCR. According to the results of IHC, the viral antigen was consistently detected in lymphocytes of bone marrow and spleen and less frequently in bronchus-associated lymphoid tissue (BALT), mesenteric lymph nodes, and Peyer's patches. Despite the antigen detection in BALT and mesenteric lymph nodes, histopathological lesions were not observed in these tissues. Lympholysis, infiltration by inflammatory cells, and increased numbers of megakaryocytes were seen in Peyer's patches, spleens, and bone marrow, respectively. In contrast to ncp BVDV-1 infection, lympholysis was found in the spleen of ncp BVDV-2-infected mice. These histopathological lesions were more severe in high-dose-inoculated mice than in low-dose-inoculated mice. CONCLUSIONS: Our results provide insight into the pathogenesis of ncp BVDV-2 infection in mice. Collectively, these results highlight significant differences in pathogenesis between ncp BVDV-1 and ncp BVDV-2 infections in a murine model.

An evaluation of circulating bovine viral diarrhea virus type 2 maternal antibody level and response to vaccination in Angus calves.

Vaccination against viruses has been shown to help prevent bovine respiratory disease in cattle. However, both passively acquired maternal antibody concentration and calf age have been shown to impact the ability of the immune system of a calf to respond to vaccination. The objectives of this study were to identify and evaluate environmental and management factors that affect 1) passively acquired bovine viral diarrhea virus (BVDV) type 2 antibody level, 2) decay rate of passively acquired BVDV type 2 antibody level, and 3) responses to BVDV type 2 vaccinations. A 2-shot modified live vaccine was administered to 1,004 Angus calves that were weaned at either the initial vaccination (n = 508) or the booster vaccination (n = 496). Calves weaned at the initial vaccination averaged 139 d whereas calves weaned at booster vaccination averaged 128 d of age. Bovine viral diarrhea virus type 2 antibodies were measured in 3 approximately 21-d intervals, serially collected serum samples to quantify antibody levels at initiation and end of vaccination protocol in addition to responses to initial, booster, and overall vaccination protocol. Amount of passively transferred antibody in the calf increased as dam age increased from 2 to 6 yr (P < 0.05) with no differences after dams reached 6 yr (P > 0.05). Calf age nested within birth year-season and dam age affected both initial and final antibody level, initial response, booster response, and overall antibody response to vaccination. The level of circulating, passively acquired maternal antibodies present at the time of vaccination had a significant (P < 0.05) negative effect on antibody responses to vaccination (initial response, booster response, and overall response). Calves that were weaned at the time of initial vaccination had significantly (P < 0.05) greater final antibody level, initial response, and overall response to vaccination than animals weaned at booster vaccination. In order for a calf to mount an overall antibody response to vaccination, maternal antibodies in circulation need to be less than 3.12 titers. However, the age at which a calf reached this antibody threshold was dependent on dam age. This information will help cattle managers and consultants design vaccination protocols to successfully mount an antibody response to vaccination.

Hemorrhagic syndrome-like disease in calves with bovine viral diarrhea and mucosal disease complex.

BACKGROUND: Bovine viral diarrhea virus (BVDV) infection is one of the causes of hemorrhagic diathesis in cattle but there have been limited field studies about that condition. HYPOTHESIS: To identify the cause of hemorrhagic diathesis in calves and describe its clinical findings. ANIMALS: Five calves from a farm with 150 dairy cows. METHODS: Clinical examination of the calves was performed. After blood samples were obtained from 2 calves, whole blood, sera, and leukocyte samples were used for hematologic and hemostatic examinations, neutralization tests, virus isolation, and viral genome sequencing. RESULTS: The calves had moderate pyrexia, dullness, serous or mucous nasal discharge, and petechial and ecchymotic hemorrhages on mucosal surfaces. Severe thrombocytopenia and anemia were identified on hematologic examinations. All calves died within 10 days of the onset of clinical signs. Virologic examinations identified BVDV as the causative agent of the disease. CONCLUSIONS AND CLINICAL IMPORTANCE: This paper identifies a hemorrhagic syndrome-like disease in calves with bovine viral diarrhea and mucosal disease complex in Turkey.