The VP4 protein from a very virulent IBDV strain antagonises type I IFN responses to a greater extent than the VP4 from a classical strain

Infectious bursal disease virus (IBDV) infects B cells in the bursa of Fabricius (BF) causing morbidity, mortality and immunosuppression in infected chickens. Classical strains (e.g. F52/70) cause 1–2 % mortality whereas very virulent strains (e.g. UK661) cause over 60 % mortality for reasons that remain poorly understood. We inoculated birds with either F52/70 or UK661, and found that the expression of pro-inflammatory and type I IFN-related genes was significantly down-regulated in UK661 compared to F52/70 infected birds ( P <0.05), despite no statistically significant difference in peak virus titres between the two strains. This was also observed in vitro in an immortalised B cell line where UK661 caused significantly reduced IFNβ and Mx1 expression compared to F52/70 ( P <0.05). The IBDV protease (VP4) has previously been reported to act as a type I IFN antagonist, although it remains unknown whether this is characteristic of all IBDVs or a strain-specific phenomenon. Using a luciferase reporter assay, we compared the IFNβ production in DF-1 cells in response to poly I:C stimulation in the presence of eGFP-VP4 expression plasmids, finding UK661 VP4 was able to down-regulate IFNβ production to a greater extent than F52/70 VP4 ( P <0.01). There are 9 amino acid differences between the two VP4 proteins and we are identifying those contributing to the observed phenotype. Taken together, our data suggest that the VP4 protein in very virulent IBDV strains evolved a greater ability to antagonise type I IFN responses than classical strains which may, in part, explain their enhanced virulence.