POLYINOSINIC-POLYCYTIDYLIC ACID (POLY I:C) INDUCES CLEARANCE OF DUCK HEPATITIS B VIRUS (DHBV) IN PEKIN DUCKS CHRONICALLY INFECTED WITH DHBV

KP Fischer, DLJ Tyrrell and KS Gutfreund

Departments of Medicine and Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta

INTRODUCTION: The use of immunomodulatory agents in the duck hepatitis B virus (DHBV) animal model has been poorly explored. The goal of this study was to assess the antiviral effect of the classical interferon (IFN) a/b inducer polyinosinic-polycytidylic acid (poly I:C) in the DHBV model.
METHODS: Pekin ducks congenitally infected with DHBV were treated with poly (I:C) 100mcg/kg/day or placebo i.v. starting at 4 weeks of age. Blood was drawn daily for analysis of serum DHBV DNA. On day ten two placebo and four poly (I:C) treated animals were harvested. Liver tissue was collected at time of termination for nucleic acid analysis. Quantitative DHBV DNA analysis was performed by real-time PCR. This in-house assay has a dynamic detection range of 10 fg/ml to 1ng/ml DHBV DNA.
RESULTS: Serum DHBV decreased in poly (I:C) compared to placebo treated animals as shown below.

Southern blot for DHBV DNA showed a modest decrease of cell associated replicative forms by day 10 in all poly (I:C) treated animals. DHBV RNA as assayed by Northern blot was concordant with the findings on Southern blot.
CONCLUSION: Up to a 1 log reduction of serum DHBV DNA was observed along with a decrease of DHBV nucleic acid species in the liver with a short course of the IFN a/b inducer poly (I:C) in ducks chronically infected with DHBV. Current analysis is examining for changes in transcript levels of avian genes involved in the immune-mediated viral clearance.