J Immunol. 2025 Oct 1;214(10):2504-2514. doi: 10.1093/jimmun/vkaf231.

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.

PMID:41169234 | DOI:10.1093/jimmun/vkaf231