Experimental WHV infection of woodchucks: an animal model of hepadnavirus-induced liver cancer

Abstract

Woodchuck hepatitis virus (WHV), a member of the Hepadnaviridae, is closely related to HBV in its virus structure, genetic organization and mechanism of replication. Natural infection of woodchucks is associated with chronic liver disease and primary hepatocellular carcinoma (HCC). A concerted effort to develop the woodchuck as an experimental animal model of hepadnavirus-induced disease was initiated in 1980. The experimental studies have established the following: (1) Chronic WHV carriage as an outcome of infection is a function of age of exposure, virus dose and, possibly, virus strain. As in humans, animals infected as newborns develop chronic antigenemia at high rates compared to young adults. (2) WHV causes primary hepatocellular carcinoma (HCC) in woodchucks. Hundred percent of experimentally-induced chronic WHsAg carriers developed HCC within three years; no HCC has occurred in concurrent uninfected control animals born and held in the same laboratory environment. The predictable course of experimental WHV infection leading to liver disease in woodchucks makes this an ideal model in which to study the natural history of hepadnavirus and to develop effective prophylactic and therapeutic strategies.