Innate host responses to Bovine Viral Diarrhea Virus

Bovine viral diarrhea virus (BVDV) is a pestivirus that suppresses the innate and adaptive host immune responses. Each of the two classified genotypes (BVDV1 and BVDV2) has two distinct biotypes – cytopathic (cp) and non-cytopathic (ncp) – and evidence has suggested that cytopathic strains may disrupt host interferon (IFN) synthesis and IFN-mediated responses. However, inconsistent results examining ncpBVDV strains have generated controversy regarding whether they also exhibit this capability. The purpose for this study was to determine the occurrence and functionality of IFN-induced responses within the serum cattle infected with ncpBVDV2-1373. Specifically, this involved analysing the changes in both the serum levels of IFN-α and IFN-γ and the expression of genes that are classically regulated by these cytokines. Serum analysis showed that the infected cattle induced both serum IFN-α and IFN-γ during BVDV infection while PBMC analysis showed increased expression of genes that classically respond to IFN-α – Mx-1, OAS-1, and STAT-1 – and IFN-γ – SOCS-1 and SOCS-3. These findings are supported by temporal kinome analysis, which verified activation of the JAK-STAT signalling network within the PBMCs of the virus-infected animals. In addition to establishing evidence for its synthesis, results from this challenge identified IFN-γ as a possible indicator of animal mortality as analysis of its change within the non-surviving, infected animals was statistically greater than the levels of the surviving, infected animals. Collectively, these results demonstrate 1373-mediated induction of, and host cell response to, both IFN-α and IFN–γ, and the potential for IFN-γ to be a predictive marker for mortality during BVDV infection