Julia F. Ridpath

Severe acute bovine viral diarrhea in Ontario, 1993-1995

In 1993, noncytopathic bovine viral diarrhea virus (BVDV) strains with enhanced virulence caused unprecedented outbreaks of severe acute bovine viral diarrhea (BVD) in dairy, beef, and veal herds in Ontario (Canada). Fever, pneumonia, diarrhea, and sudden death occurred in all age groups of cattle. Abortions often occurred in pregnant animals. Gross lesions in the alimentary tract were similar to those associated with mucosal disease, especially in animals >6 months of age. Cattle of all age groups had microscopic lesions in the alimentary tract similar to those seen with mucosal disease. The epidemic peaked in the summer of 1993, with 15% of all bovine accessions from diseased cattle presented to the diagnostic laboratory being associated with BVDV. The virus strains involved in the outbreak were analyzed using monoclonal and polyclonal antibodies and the polymerase chain reaction. The virus isolates from these outbreaks of severe disease were determined to be type 2 BVDV. Type 2 BVDV has been present in Ontario at least since 1981 without causing widespread outbreaks of severe acute BVD, which suggests that type 2 designation in itself does not imply enhanced virulence. Cattle properly vaccinated with type 1 BVDV vaccines appear to be protected from clinical disease.

Methods for Detection and Frequency of Contamination of Fetal Calf Serum with Bovine Viral Diarrhea Virus and Antibodies against Bovine Viral Diarrhea Virus

Methods used by the National Animal Disease Center to test fetal calf serum for contamination with bovine viral diarrhea virus (BVDV) and antibodies against BVDV are described. Using those methods, virus was isolated from 332 of 1,608 (20.6%) lots of raw fetal calf serum obtained specifically for the Center and 93 of 190 (49%) lots of commercially available fetal calf serum. Virus neutralization and immunoperoxidase staining tests were used to detect antibodies against BVDV in 224 of the 1,608 (13.9%) lots of raw fetal calf serum. Both BVDV and antibodies against BVDV were detected in 50 lots of raw serum. The molecular specificity of antibodies against BVDV was determined by radioimmunoprecipitation. Lots of fetal calf serum that contained BVDV-specific antibodies that did not neutralize virus were identified.

Monoclonal antibodies with neutralizing activity segregate isolates of bovine viral diarrhea virus into groups

SummaryIsolates of bovine viral diarrhea (BVD) virus were differentiated by monoclonal antibodies (MoAbs) reactive with the 56kD viral polypeptide. Patterns of neutralizing activity of the MoAbs indicate that multiple epitopes are involved in virus neutralization.

Bovine Viral Diarrhea Virus: Diagnosis, Management, and Control

Contributors. Preface. 1. Introduction and History. (Dirk Deregt). 2. Distribution and Prevalence. ( Hans Houe). 3. Virus Classification and Molecular Virology. (Julia F. Ridpath). 4. Virus Replication. (S. K. Hietala and B.M. Crossley). 5. Virus Transmission. (Mark C. Thurmond). 6. Clinical Features. (James F. Evermann and George M. Barrington). 7. Pathogenesis. (E. Liebler-Tenorio). 8. Reproductive Disease and Persistent Infections. (Kenny V. Brock, Daniel L. Grooms, and M. Daniel Givens). 9. Immunity and Immunosuppression. (Sanjay Kapil, Paul Walz, Melinda Wilkerson and Harish Minocha). 10. Hosts. (Trevor R. Ames). 11. Interactions of Virus and Host. (John D. Neill). 12. Diagnosis. (Sagar M. Goyal). 13. Vaccines. (Robert L. Fulton). 14. Management Systems and Control Programs. (Robert L. Larson). 15. Conclusions and Future Research. (Julia F. Ridpath and Sagar M. Goyal). Index.

Maternal Antibody Blocks Humoral but Not T Cell Responses to BVDV

Bovine viral diarrhoea virus (BVDV) contributes significantly to health-related economic losses in the beef and dairy industry. Antibodies of maternal origin can be protective against BVDV infection, however, calves with low titres of maternal antibody or that do not receive colostrum may be at risk for acute BVDV infection. Interference by high titres of maternal antibodies prevents the development of an antibody response following vaccination with either a killed or attenuated BVDV vaccine. However, the T cell mediated immune response to BVDV may be generated in the absence of a detectable serum neutralizing antibody response. Two trials were conducted to evaluate the potential to elicit T cell mediated immune responses to BVDV in calves with circulating maternal antibody to BVDV. In the first trial, calves with high levels of circulating maternal antibody to BVDV 1 and BVDV 2 were experimentally infected with BVDV 2 (strain 1373) at two to five weeks of age. The T-cell mediated immune responses of the experimentally infected calves and non-infected calves were monitored monthly until circulating maternal antibody was no longer detectable in either treatment group. Calves experimentally infected with BVDV developed BVDV specific CD4(+), CD8(+), and delta T cell responses while high levels of maternal antibody were circulating. A second challenge with BVDV 2 (strain 1373) was performed in the experimentally infected and control calves once maternal antibody could no longer be detected. Previous exposure to BVDV in the presence of maternal antibody protected calves from clinical signs of acute BVDV infection compared to the control calves. In the second trial, three groups of calves with circulating maternal antibody to BVDV were given either a modified live vaccine (MLV) containing BVDV 1 and BVDV 2, a killed vaccine containing BVDV 1 and BVDV 2, or no vaccine, at seven weeks of age. Serum neutralizing antibody levels and antigen specific T cell responses were monitored for 14 weeks following vaccination. Calves vaccinated with MLV BVDV developed BVDV 1 and BVDV 2 specific CD4(+)T cell responses, and BVDV 2 specific gammadelta T cell responses, in the presence of maternal antibody. Vaccination with killed BVDV did not result in the generation of measurable antigen specific T cell immune responses. In this trial, a second vaccination was performed at 14 weeks to determine whether an anamnestic antibody response could be generated when calves were vaccinated in the presence of maternal antibody. Calves vaccinated with either a MLV or killed BVDV vaccine while they had maternal antibody developed an anamnestic antibody response to BVDV 2 upon subsequent vaccination. The results of these trials indicate that vaccinating young calves against BVD while maternal antibody is present may generate BVDV specific memory T and B cells. The data also demonstrated that seronegative calves with memory T and B cells specific for BVDV may be immune to challenge with virulent BVDV.

Bovine Viral Diarrhea Virus: Global Status

Despite the success of regional bovine viral diarrhea viruses (BVDV) eradication programs, infections remain a source of economic loss for producers. The wide variation among BVDV results in differences in genotype, biotype, virulence, and types of infections. BVDV infect a range of domestic and wild ruminants. Clinical presentation varies depending on strain of virus, species of host, immune status of host, reproductive status of host, age of host, and concurrent infections. Recent advances in BVDV research and diagnostics have led to the development of regional eradication/control programs, the most efficacious of which focus on biosecurity, surveillance, and control.

Prevalence of bovine viral diarrhea virus genotypes and antibody against those viral genotypes in fetal bovine serum

One thousand lots of pooled fetal bovine serum (FBS) were tested for contamination with bovine viral diarrhea virus (BVDV) and/or for contamination with neutralizing antibody against BVDV. Noncytopathic or cytopathic BVDV was isolated from 203 lots of FBS. Analysis of the viral isolates identified 115 type 1 and 65 type 2 BVDV isolates. An additional 23 virus isolates were mixtures of >2 BVDV isolates and were not classified to viral genotype. Further characterization of the type 1 viruses identified 51 subgenotype 1a and 64 subgenotype 1b BVDV isolates. Viral neutralizing antibody was detected in 113 lots of FBS. Differential viral neutralization indicated that type 1 BVDV induced the antibody detected in 48 lots of FBS and type 2 BVDV induced the antibody detected in 16 lots of FBS.

Survey of cell lines in the American Type Culture Collection for bovine viral diarrhea virus

Cell lines originating from cattle, sheep, goat, deer, bison, swine, rabbit, hamster, cat, dog, monkey, human, and mosquito were obtained from the American Type Culture Collection and tested for contamination with bovine viral diarrhea virus (BVDV). Immunocytochemical procedures and polymerase chain reaction (PCR) amplification were used to detect viral antigen or viral RNA in 13 of 41 cell lines. The results of these procedures correlated exactly. Cell lines derived from cattle, sheep, goat, deer, bison, rabbit, and domestic cat were found contaminated with BVDV. Attempts were made to experimentally infect 14 swine, rabbit, hamster, cat, dog, monkey, and human cell lines that had been found free of virus. All swine cell lines, and most rabbit and cat cell lines, became infected with BVDV. Hamster, human, dog, and certain rabbit and cat cells were refractory to BVDV infection. Experimental infection of monkey cells produced variable results.

Changes in Levels of Viremia in Cattle Persistently Infected with Bovine Viral Diarrhea Virus

Virus isolation and serum neutralizing antibody titers were determined over a period of time from samples collected from animals persistently infected with bovine viral diarrhea virus (BVDV). To evaluate over time the ability to detect BVDV by virus isolation from serum or white blood cell preparations, 4 persistently infected calves were monitored from birth until 70 days of age. In 3 of 4 persistently infected calves, virus isolation from serum and white blood cells was negative until approximately 42 days of age, when colostral antibody had declined. The level of viremia in 7 adult (>12 months) persistently infected animals decreased by 1 10-fold dilution over at least a 2-year period. The level of viremia became undetectable by virus isolation from serum in 1 of the 7 animals examined. This decline was associated with the development of virus neutralizing antibody. Although the level of viremia is fairly stable within persistently infected animals, the presence of specific neutralizing antibody may affect the ability to isolate BVDV. These findings are important when considering diagnostic testing to identify persistently infected animals by virus isolation.

Prevalence and Antigenic Differences Observed between Bovine Viral Diarrhea Virus Subgenotypes Isolated from Cattle in Australia and Feedlots in the Southwestern United States

Bovine viral diarrhea virus (BVDV) is divided into 2 different species within the Pestivirus genus, BVDV type 1 (BVDV-1) and BVDV type 2 (BVDV-2). Further phylogenetic analysis has revealed subgenotype groupings within the 2 types. Thus far, 12 BVDV-1 subgenotypes (a–l) and 2 BVDV-2 subgenotypes (a and b) have been identified. The purpose of the current study was to determine the prevalence of BVDV subgenotypes in the United States and Australia and to determine if there are detectable antigenic differences between the prevalent subgenotypes. To determine prevalence, phylogenetic analysis was performed on 2 blinded panels of isolates consisting of 351 viral isolates provided by the Elizabeth Macarthur Laboratory, New South Wales, and 514 viral isolates provided by Oklahoma State University. Differences were observed in the prevalence of BVDV subgenotypes between the United States (BVDV-1b most prevalent subgenotype) and Australia (BVDV-1c most prevalent subgenotype). To examine antigenic differences between the subgenotypes identified in samples from the United States and Australia, polyclonal antisera was produced in goats by exposing them at 3-week intervals to 2 noncytopathic and 1 cytopathic strain of either BVDV-1a, BVDV-1b, BVDV-1c, BVDV-2a, or Border disease virus (BDV). Virus neutralization (VN) assays were then performed against 3 viruses from each of the 5 subgenotypes. Comparison of VN results suggests that there are antigenic differences between BVDV strains belonging to different subgenotypes. The present study establishes a foundation for further studies examining whether vaccine protection can be improved by basing vaccines on the BVDV subgenotypes prevalent in the region in which the vaccine is to be used.