An outbreak of bovine viral diarrhoea/mucosal disease

Extract

The following is a report of an outbreak of bovine viral diarrhoea/mucosal disease affecting a mob of 13 Hereford yearling bulls.     

Infection of ovine fetal brain cell cultures with cytopathogenic and non-cytopathogenic bovine viral diarrhoea virus.

The in vitro cell tropism of non-cytopathogenic (ncp) and cytopathogenic (cp) bovine viral diarrhoea virus (BVDV) was studied in primary dissociated brain cell cultures derived from ovine fetuses of different gestational ages. The cell types infected were identified by double immunofluorescence using antibodies against BVDV and cell type-specific markers. In cultures infected with ncp BVDV viral antigen was present in neurofilament (NF 200 kDa)-positive neurons, glial fibrillary acidic protein (GFAP)-positive astrocytes and fibronectin-expressing cells. Estimation of the percentages of individual cell types infected with ncp BVDV indicated a tropism for NF 200-positive neurons. In cultures infected with cp BVD virus cytopathic changes were observed beginning at 40 hours post infection. Viral antigen was present in vacuolated NF 200-, GFAP- and fibronectin-positive cells. In comparison with non-infected control cultures a considerable reduction of the number of the different cell types was seen.     

Serological comparison of cytopathogenic and non-cytopathogenic bovine viral diarrhea-mucosal disease viruses isolated from cattle with mucosal disease

Ten cattle that died with mucosal disease were examined for bovine viral diarrhea-mucosal disease (BVD-MD) viruses. Both cytopathogenic (CP) and non-cytopathogenic (NCP) BVD-MD viruses were isolated concomitantly from 9 of them, and only a CP virus was recovered from the other. Then each pair of CP and NCP viruses was compared serologically by a serum neutralization test. Each pair of CP and NCP viruses from the same cattle was found to be serologically indistinguishable, although a minor antigenic difference was observed among the groups of the paired viruses. These results seem to support the hypotheses that mucosal disease occurs in persistently infected cattle which were induced by in utero infection with NCP virus when they are superinfected with CP virus, and the antigenic homology in CP and NCP BVD-MD viruses may be an important factor in the pathogenesis of the disease.     

Comparison by the neutralisation assay of pairs of non-cytopathogenic and cytopathogenic strains of bovine virus diarrhoea virus isolated from cases of mucosal disease

Neutralising antibody to non-cytopathogenic and cytopathogenic strains of bovine virus diarrhoea virus (BVDV) was assayed in a microtitre test in which cultures of calf testis cells were stained by the immunoperoxidase method to detect viral replication. Fourteen BVDV strains were compared in cross neutralisation tests with antisera prepared in gnotobiotic calves. Ten of the strains comprised five pairs of non-cytopathogenic and cytopathogenic BVDV. Each pair was isolated from an animal with mucosal disease. All five animals were from five separate outbreaks of the disease. Each pair of strains from the same outbreak was found to be antigenically indistinguishable. In contrast, when the coefficient of antigenic similarity was calculated 11 of 45 comparisons between the pairs and 46 of 91 comparisons between all 14 viruses gave R values that distinguished strains. The observations suggest that an antigenic spectrum within a single related group exists for BVDV strains, rather than distinct serotypes. The findings are also consistent with the suggestion that cytopathogenic strains from natural outbreaks of mucosal disease arise by mutation from non-cytopathogenic virus.     

Pathogenesis of mucosal disease and molecular aspects of bovine virus diarrhoea virus

Studies carried out over three decades, on the pathogenesis and epidemiology of bovine virus diarrhoea virus (BVDV), have provided the basis for our understanding of the aetiology of mucosal disease. Experimental reproduction of the disease has demonstrated the mechanism of sequential infection and the role of the two virus biotypes. The need for "homogeneity" between the biotypes, causing mucosal disease, has demonstrated the precision of immunotolerance. The origin of the cytopathogenic biotype remains unclear but molecular studies may provide the solution. Recent findings have revealed the absence of an 80 kDa polypeptide in the non-cytopathogenic isolates. This protein is related to the 120 kDa polypeptide that is present in both biotypes. Genomic sequences for two isolates have been reported. An extensive homology to the protein ubiquitin has been identified only within the Osloss sequence in the region flanking coding sequences for the 80 kDa and 120 kDa proteins. Advances in the development of molecular gene probes and monoclonal antibodies will provide new tools for furthering our understanding of the pathogenesis, epidemiology and interrelationships of pestiviruses that infect pigs, cattle and sheep.     

Differential activation of interferon regulatory factors-3 and -7 by non-cytopathogenic and cytopathogenic bovine viral diarrhoea virus

Non-cytopathogenic bovine viral diarrhoea virus (ncpBVDV) has previously been shown to inhibit the function of interferon regulatory factor-3 in cultured cells [J. Virol. 76 (2002) 8979]. In this study, we show that, like ncpBVDV, when cells were previously exposed to cytopathogenic BVDV (cpBVDV) the appearance of an IRF-3–DNA complex from nuclear extracts that can be induced by heterologous virus infection was not observed. Infection of cells with ncpBVDV or cpBVDV resulted in neither the translocation of IRF-7 from the cytoplasm to the nucleus of infected cells, nor an inhibition of its nuclear translocation in cells super-infected by Semliki Forest Virus. We conclude that cpBVDV and ncpBVDV both share the ability to inhibit the full function of IRF-3 but neither stimulate or block the nuclear uptake of IRF-7.     

Antibodies to bovine viral diarrhoea virus in beef cattle

Infection of cattle with bovine viral diarrhoea virus (BVD virus) is common throughout the world(1) and the prevalence of neutralising antibodies to the virus reported from surveys ranges from about 40% to 90%(2)(3)(4). The first isolation of BVD virus in New Zealand was reported in 1967(5) and, since that time, evidence of widespread infection in dairy cattle has been presented(6). Whilst the diseases associated with BVD viral infection have been well recognised in dairy herds, there has been a belief that infection of beef herds is less common. Based on this belief has been the fear that the growth of the dairy beef industry could lead to the introduction of BVD virus into an essentially naive beef population with disastrous results such as those reported by MacNeil and van der Oord⁽⁷⁾. We decided therefore to sample beef cattle submitted to abattoirs throughout New Zealand for serological evidence of prior exposure to BVD virus.     

Persistent bovine viral diarrhoea virus infection in US beef herds

In the summer of 1996, we screened 18,931 calves in 128 beef herds located in five US states for persistent bovine viral diarrhea virus (BVDV) infection. Of these, 76 herds were randomly selected from the client database of collaborating veterinary practices, and 52 herds were suspected by the collaborating veterinarians to have BVDV infection based on history or clinical signs. Serum was obtained from each calf in the cooperating herds prior to 4 months of age and tested for the presence of BVDV by microtiter virus isolation. Information about each of the herds (including management practices, vaccination history, and breeding- and calving-season production measures) were collected by the collaborating veterinarians using standardized questionnaires. A total of 56 BVDV-positive calves in 13 herds were identified on initial screening. Ten (19%) of the BVDV-suspect herds and three (4%) of the randomly selected herds had > or = 1 BVDV-positive calf at initial screening. Multiple BVDV-positive calves were identified in 10 of those 13 herds. Follow-up information was obtained for 54 of the 56 positive calves. Ten out of 54 (18%) died prior to weaning, and 1 (2%) was sold because of unusually poor growth. Thirty-three out of 54 (61%) of the initially positive calves remained BVDV positive at 6 months of age - confirming persistent-infection (PI) status. Dams of 45 of the 56 positive calves were tested, with 3 (7%) identified as positive - indicating most PI calves were products of acute dam infection during gestation. The proportion of cows that were pregnant at the fall 1995 pregnancy examination was 5% lower in herds with PI calves born during the 1996 calving season than in randomly selected herds without PI calves. Most of the calves we identified with persistent BVDV infections survived to weaning, and could provide a constant source of virus to the herd throughout the breeding season and early gestation.     

Experimental inoculation of pregnant swine with type 1 bovine viral diarrhoea virus

The ability of bovine viral diarrhoea virus type 1 (BVDV-1) to induce transplacental infection in pigs was evaluated. Control pigs (n = 4) were sham-inoculated while infected pigs (n = 4) were intranasally inoculated with BVDV-1 on day 65 of gestation. Blood samples were tested throughout the study for BVDV and antibody to BVDV. On day 110 of gestation, a Caesarean section was performed. Serum was obtained for virus isolation and antibody determination from all piglets, and all experimental animals were killed. Tissues were collected for virus isolation and histopathology. Bovine viral diarrhoea virus was isolated on days 5 and 7 after infection and seroconversion was demonstrated in all infected gilts; however, BVDV was only isolated from one fetus from an infected pig. Viraemia and seroconversion were demonstrated in the pregnant gilts; however, transplacental infection at day 65 of gestation in the pig was not consistently demonstrated.