Frequency of bovine viral diarrhea virus detected in subpopulations of peripheral blood mononuclear cells in persistently infected animals and health outcome

Authors: Falkenberg, Shollie; Dassanayake, Rohana; WALZ, PAUL - Auburn University; Casas, Eduardo; Neill, John; Ridpath, Julia

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/23/2018
Publication Date: 1/1/2019
Citation: 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.
DOI: https://doi.org/10.1016/j.vetimm.2018.11.015

Interpretive Summary: Bovine viral diarrhea virus (BVDV) can cause both acute and persistent infections, but the immune responses associated with each of these infections differ. Acute infections generally are associated with a decrease in circulating lymphocytes, but persistent infections with BVDV is the result of immune tolerance to the virus and is generally not associated with a decrease in circulating lymphocytes. The health outcome of persistently infected (PI) calves varies widely; some die of mucosal disease, some succumb to ill thrift and others appear normal and survive to adulthood. The outcome of PI calves is likely due to a break in immune tolerance to the persisting virus. Data from this study demonstrated that calves died over the course of the sampling period of 3 months, were found to have no or little virus in a specific lymphocyte population (T cells). The clearance of virus from the specific lymphocyte population suggests a breakdown in immune tolerance in these calves. This is the first report of a pattern observed in the viral load in specific immune cell and survival in PI calves.

Technical Abstract: 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 of CD4+ and CD8+ T cell populations. Persistent infection with BVDV is the result of immune tolerance and is generally not associated with lymphocytopenia. The health outcome of persistently infected (PI) calves varies widely; some die of mucosal disease, some succumb to ill thrift and others appear normal and survive to adulthood. Detection of BVDV at the single lymphoid 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 the single cell level. To circumvent this difficulty, a novel flow cytometry-based PrimeFlow RNA assay using in-situ detection of BVDV was developed. 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 (type 1 and type 2). Calves were sampled at 3 different time points approximately one month apart. During the course of the study, a subset of the calves died from ill thrift. Mucosal disease was not indicated in any of the deaths. Using RNA probes specific for the BVDV Npro-Erns coding regions for each respective virus, BVDV RNA was detected in all PBMC of PI that appeared clinically healthy. Calves that succumbed to ill thrift were found to have no or little virus in T cells. The clearance of virus from T cells suggests a breakdown in immune tolerance in these calves. This is the first report of a pattern observed in the viral load in the T cell subpopulations and survival in PI calves.