Localization of woodchuck hepatitis virus in liver tissue from 10 infected woodchucks was investigated immunohistochemically and ultrastructurally. Woodchuck hepatitis virus surface antigen was detected by immunoperoxidase methods in the cytoplasm of hepatocytes with a fine granular and/or inclusion body appearance. Woodchuck hepatitis virus surface antigen positive hepatocytes were often found in the peripheral zone of hepatic lobules. In contrast to human hepatitis B core antigen, woodchuck hepatitis virus core antigen was observed only in the cytoplasm of hepatocytes, but not in the nuclei. In hyperplastic foci, woodchuck hepatitis virus antigen-positive hepatocytes were found in 3 of 8 animals. Furthermore, in 1 of 5 animals with hepatocellular carcinoma, woodchuck hepatitis virus surface antigen and woodchuck hepatitis virus core antigen were present in carcinoma cells. Electron microscopic examination revealed many filamentous structures (18 to 20 nm in diameter) in the cisternae of the endoplasmic reticulum. Noncoated core particles (18 to 20 nm in diameter) were found in the cytoplasm of the hepatocytes, but not in the nuclei. The coated particles (42 to 46 nm in diameter) were observed in the cisternae of the endoplasmic reticulum. These coated particles were shown to be morphologically identical to the virus particles in serum. These results indicate that woodchuck hepatitis virus core antigen is produced and assembled mainly in the cytoplasm of hepatocytes, and seems to be rapidly assembled into virion. The similarity of woodchuck hepatitis vicus infection to human hepatitis B virus infection makes the woodchuck an excellent experimental model for the study of hepadna virus oncogenesis.
Woodchuck hepatitis virus (WHV) was first recognized in 1978 as a new member of t h e virus family called hepadna viruses (1). The WHV has been shown t o be similar t o human hepatitis B virus (HBV) with immunological cross-reactivity and significant DNA homology (2, 3). WHV is highly oncogenic; chronic infection with WHV leads to hepatocellular carcinoma in more t h a n half of infected animals (4, 5). Thus, the woodchuck (Murrnotu rnonm) has become a n important laboratory animal increasingly for the study of human hepatitis B and HBV-induced hepatocellular carcinoma. T h e pres-