Association between bovine viral diarrhea virus load in subsets of peripheral blood mononuclear cells (PBMC) in persistently infected animals and health outcome

Abstract

Abstract Bovine viral diarrhea virus (BVDV) can cause acute and persistent infections. BVDV acute infection results in generalized immunosuppression characterized by lymphocytopenia typically associated with depletion of CD4+ and CD8+ T cells. BVDV persistent infection is the result of immune tolerance and is 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 survive to adulthood. Detection of BVDV at the single lymphoid cell level is important to the study of subsets of PBMC in acute and persistent 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 PrimeFlow RNA assay using in-situ detection of BVDV was developed. This assay was used to evaluate differences in viral distribution within subsets 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 at least 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 region 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 an association between viral load in the T cell populations and survival in PI calves.