| Two approaches to enhance infectious bursal disease virus (IBDV) resistance in chickens were evaluated: major histocompatibility (MHC) as a potential marker of disease resistance in broilers and anti-viral treatment with dicationic molecules. Chickens with different MHC haplotypes from a commercial broiler line were compared for their susceptibility to IBDV. A model was developed to determine the best measure(s) of infectious bursal disease severity and the optimum dose of IBDV to allow the detection of resistance due to genetic differences. Historically, bursa weight has been used to assess IBD damage. However, this work demonstrated that bursa cell count is a more reliable and quantitative measure than bursa weight for assessing bursa damage due to IBDV infection even at low doses. Both APHIS and Variant E strains showed a dose-related effect on bursa cell counts as early as 3 days post-infection (p.i.).; Despite the significant reduction of lymphocytes in the bursa at 3 days post-infection, there was no detectable influx of T-cells, with the exception of the highest dose of Variant E. Therefore, T-cells may not be responsible for bursa cell loss. There was no consistent difference in viral load (3 days p.i.), bursa lymphocyte count (3 days or 10 days p.i.), or bursa histological lesion score (3 or 10 day p.i.), among the MHC genotypes tested.; Studies regarding antiviral treatment were begun with an in vitro chick embryo fibroblast cell culture assay. Incubation with aromatic diamidine compounds resulted in a substantial reduction in viral titers for the Delaware Variant A strain of IBDV. Active compounds affected virion formation in a dose dependent fashion. The compound designated SW066 appeared to interfere early in the virus life cycle at a stage after attachment and penetration, but before virion formation, e.g., uncoating, viral protein expression or viral genome replication. A trypsin competition experiment showed that drug activity did not occur via a trypsin-like protease-mediated mechanism of virus attachment or penetration. Drug removal studies showed that their activity occurs after attachment and penetration.; Compounds found to be most active in vitro (DB197, DB203 and DB528) were selected to treat IBDV infected specific pathogen free White Leghorns. These drugs exhibited a higher level of bursal protection as measured by bursa cell count at 3 days p.i. IBDV infected birds treated with DB197 demonstrated a low bursa cell reduction, 26.5% relative to the uninfected control. (Abstract shortened by UMI.)... |
