Molecular species of hepadnavirus core and envelope polypeptides in hepatocyte plasma membrane of woodchucks with acute and chronic viral hepatitis

Hepadnaviral antigens exposed on hepatocytes serve as targets and as possible modulators of immunopathogenic reactions causing liver damage. To identify molecular species of viral proteins at the liver cell surface and the relationship between their expression and the persistence and severity of virus‐induced liver injury, we examined woodchuck hepatitis virus core and envelope polypeptides in host hepatocyte plasma membranes from acute and chronic hepatitis. Western blot analysis revealed that two virus core polypeptides with a molecular mass of 22 kD and 43 kD occur in the membranes of infected animals. The molecular profiles and the membrane levels of the core antigen were not related to the duration or histological severity of liver damage. In contrast, quantities of the virus surface antigen were significantly greater in hepatocyte membranes of animals with chronic hepatitis. The envelope preS1, preS2 and S polypeptides, with or without molecularmass equivalents in the subviral surface antigen particles and virions, were detected in all infected membranes, although the preS2 polypeptides were always dominant. Our findings indicate that hepadnavirus core and envelope polypeptides are integral constituents of hepatocyte membranes in the course of hepatitis. They demonstrate that the accumulation of viral envelope proteins, predominantly the S‐domain sequences, in hepatocyte membranes is a prominent characteristic of chronic hepatitis. This event might contribute to promotion of development and maintenance of hepadnavirus‐related chronic liver disease. (Hepatology 1994;20:275‐286.)