Inflammatory cytokines induced by Bovine Viral Diarrhoea Virus (BVDV) in Peripheral Blood Mononuclear Cell (PBMC) subsets
Bovine viral diarrhoea virus (BVDV) is the causative agent of a complex of disease syndromes in cattle with high economical and welfare impacts. BVDV occurs as two biotypes; cytopathic (BVDVcp) and noncytopathic (BVDVncp) determined by differential effects on cultured cells and can also be divided into two genotypes (BVDV1 and BVDV2) on the basis of genomic diversity. The interaction between BVDV and the host?s immune system is regarded a key aspect in the sequel of BVDV infection. Infection with BVDV normally causes an acute transient infection, with mild to subclinical signs, but occasionally results in severe and even fatal disease. More importantly, BVDVncp virus can cause persistent infections, evading both the adaptive immunity as well as important mechanisms of the innate immunity. In the present study, attempts were made to compare the effect of a BVDVncp infection on bovine monocyte-derived dendritic (mDCs) cells on their ability to produce IFN?/?, IL-10 and IL-12. To potentially assess strain-variabilities, two different type 1 BVDVncp strains were used, one associated with mild acute disease and the other one with severe acute disease. This study confirms previously published data demonstrating that mDCs are susceptible to BVDVncp infection which implicates the potential of BVDVncp to affect the functions of this important antigen presenting cell. Unfortunately no conclusive data was obtained from quantitative polymerase chain reaction for mRNA expression levels of IL-10 and IL-12. Production of IFN?/? was measured in supernatants from stimulated mDCs and consistent with existing data no notable levels of IFN?/? could be detected. To further investigate how BVDVncp interact with the IFN?/? response in mDCs, protein levels of the transcription factors interferon regulatory factor 3 (IRF3) and interferon regulatory factor 7 (IRF7) were investigated by Western blotting. Here, the strain causing a more severe disease form seemed to be able to interfere with IRF3 protein levels differentially compared to the strain inducing a mild disease form. Thus, the data indicate that BVDVncp may interact in more than one way with the IFN?/? pathway, potentially by inhibiting IRF3 activity, and that these differences could be strain-specific and potentially linked to disease severity.