Location: Ruminant Diseases and Immunology Research
2019 Annual Report
Accomplishments
1. Association of numbers of small noncoding RNAs in bovine leukemia virus infection. Bovine leukemia virus (BLV) affects cattle health and productivity worldwide, causing abnormal immune function and immunosuppression. The objective of this study, conducted by ARS researchers at Ames, Iowa, was to identify specific small non-coding RNAs associated with an antibody response to BLV in Holstein cattle. Sera from 14 animals were collected to establish amount of antibody against BLV by ELISA. Seven animals were seropositive (positive group) and seven were seronegative (negative group) for BLV exposure. Leukocytes from each animal were collected and the noncoding RNAs were extracted for sequencing. Three of these RNAs were significantly different between seropositive and seronegative groups (P < 0.0067). In all cases the positive group had a lower number of these RNAs when compared to the negative group. This research will benefit researchers investigating the pathogenesis of disease and new methods to detect BLV infections in cattle.
2. Neutralization of bovine viral diarrhea viruses with vaccine virus antiserum. Bovine viral diarrhea virus (BVDV), a common pathogen of cattle, causes subclinical to severe acute disease. Two species of BVDV are recognized, BVDV1 and BVDV2 with BVDV1 divided into at least 21 subgenotypes and BVDV2 into 3-4 subgenotypes, most commonly using sequences from the 5' untranslated region (5' UTR). A study conducted by ARS researchers at Ames, Iowa, reported whole genomic sequencing of 8 BVDV2 isolates that were not BVDV2a; but represented two additional BVDV2 subgenotypes. One BVDV2 subgenotype was previously recognized only in Asia. The other seven viruses fell into a second subgenotype that was first reported in Brazil and the U.S. in 2002. Neutralization assays using antiserum raised against vaccine strain BVDV2a 296c revealed varying degrees of neutralization of genetically distant BVDV2 isolates. Neutralization titers decreased from almost 2-fold to a more than 18-fold decrease, showing that vaccine viruses produced variable protection. This study illustrated the considerable genetic and antigenic diversity in BVDV2 circulating in the U.S. and demonstrates a need for more comprehensive immune coverage than what current commercial vaccines provide.
3. Use of a new technique to study bovine viral diarrhea virus infection in bovine peripheral blood mononuclear cells (PBMCs). Bovine viral diarrhea viruses (BVDV) cause acute and persistent infections. Acute infection results in generalized immunosuppression characterized by a decrease in circulating lymphocytes as a result of depletion T cell populations. Persistent infection with BVDV is the result of immune tolerance and is generally not associated with decreased lymphocyte numbers. The health outcome of persistently infected (PI) calves varies widely; some die of mucosal disease (a rare form of disease caused by BVDV), some succumb to ill thrift and others appear normal and survive to adulthood. Detection of BVDV at the single cell level is important to the study of subpopulations of peripheral blood mononuclear cells (PBMC) during BVDV infections, however there are few methods available for the detection and quantification of BVDV at this level. A study conducted by ARS researchers at Ames, Iowa, developed a novel flow cytometry-based RNA assay using in-situ detection of BVDV. This assay was used to evaluate differences in viral distribution within subpopulations of PBMC over time in PI calves carrying one of two different species of BVDV (BVDV1 and BVDV2). Clearance of virus from T cells indicated a breakdown in immune tolerance in these calves. This was the first report of a pattern observed in the viral load in the T cell subpopulations and survival in PI calves. This research will benefit researchers investigating the pathogenesis of disease caused by BVDV.
4. New animal model for the study of respiratory syncytial virus infection. Respiratory syncytial virus (RSV) is a significant cause of pediatric respiratory tract infections. It is estimated that two-thirds of infants are infected with RSV during the first year of life and it is one of the leading causes of death in this age group worldwide. Similarly, bovine RSV is a primary viral pathogen in cases of pneumonia in young calves and plays a significant role in bovine respiratory disease complex. Importantly, naturally occurring infection of calves with bovine RSV shares many features in common with human RSV infection. ARS researchers at Ames, Iowa, provided new information to increase the current understanding of RSV infection in cattle, by providing new methods of vaccination. The recent reports in which the neonatal calf was employed for the development and testing of vaccines and therapeutics which may be applied to hRSV infection in humans. This research will benefit researchers and vaccine companies investigating better ways to vaccinate against RSV in cattle and humans.
Review Publications
Falkenberg, S.M., Dassanayake, R.P., Walz, P., Casas, E., Neill, J.D., Ridpath, J.F. 2019. Frequency of bovine viral diarrhea virus detected in subpopulations of peripheral blood mononuclear cells in persistently infected animals and health outcome. Veterinary Immunology and Immunopathology. 207:46-52. https://doi.org/10.1016/j.vetimm.2018.11.015.
Imus, J.K., Lehmkuhl, H.D., Woods, L.W. 2018. Resistance of colostrum-deprived domestic lambs to infection with deer adenovirus. Journal of Veterinary Diagnostic Investigation. 31(1):78-82. https://doi.org/10.1177/1040638718817508.
Register, K.B., Olsen, S.C., Sacco, R.E., Ridpath, J., Falkenberg, S., Briggs, R., Kanipe, C., Madison, R. 2018. Relative virulence in bison and cattle of bison-associated genotypes of Mycoplasma bovis. Veterinary Microbiology. 222:55-63. https://doi.org/10.1016/j.vetmic.2018.06.020.
Powell, E.J., Reinhardt, T.A., Casas, E., Lippolis, J.D. 2018. The effect of pegylated granulocyte colony-stimulating factor treatment prior to experimental mastitis in lactating Holsteins. Journal of Dairy Science. 101(9):8182-8193. https://doi.org/10.3168/jds.2018-14550.
Dassanayake, R.P., Falkenberg, S.M., Register, K.B., Samorodnitsky, D., Nicholson, E.M., Reinhardt, T.A. 2018. Antimicrobial activity of bovine NK-lysin-derived peptides on Mycoplasma bovis. PLoS One. 13(5):e0197677. https://doi.org/10.1371/journal.pone.0197677.
Guerra-Maupome, M., Palmer, M.V., McGill, J.L., Sacco, R.E. 2019. Utility of the neonatal calf model for testing vaccines and intervention strategies for use against human RSV infection. Vaccines. 7(1):7. https://doi.org/10.3390/vaccines7010007.
Taxis, T.M., Kehrli Jr., M.E., D'Orey-Branco, R., Casas, E. 2018. Association of transfer RNA fragments in white blood cells with antibody response to bovine leukemia virus in Holstein cattle. Frontiers in Genetics. 9:236. https://doi.org/10.3389/fgene.2018.00236.
