Immunological aspects of naturally occurring model of hepatitis B virus (HBV) infection, hepatitis B, and HBV-associated hepatocellular carcinoma in the American woodchuck Marmota monax.

Abstract

Infection of eastern North American woodchucks (Marmota monax) with woodchuck hepatitis virus (WHV) represents the most valuable immunopathogenic model of hepatitis type B that, like in humans, can advance stepwise from acute hepatitis to chronic hepatitis and hepatocellular carcinoma (HCC) or become self-resolving and persist as a clinically asymptomatic infection throughout the lifespan. This naturally occurring model is utilized for both basic research and preclinical assessments of anti-hepatitis B virus (HBV) agents and immunotherapies against chronic hepatitis B and HCC. The main advantages of the system include a close molecular and immunogenic compatibility between HBV and WHV, equivalence in immune responses in different forms of infection and stages of hepatitis, human-compatible responsiveness to antivirals and immunotherapies, and the fact that virus-host interactions occur in an innately virus-susceptible, immunologically intact host. Woodchuck-WHV infection offers a well-characterized and all-inclusive system to advance studies on HBV pathogenicity and oncogenicity, and for discovery and preclinical validations of new therapies.