Woodchuck Hepatitis Virus Hepatocyte Culture Models

Hepatocytes are the site of the most vigorous replication and virion assembly in the course of a serologically evident hepadnavirus infection. They also support persistent propagation of small quantities of hepadnavirus that continues as a serologically unapparent (occult) infection long after resolution of hepatitis or due to a primary silent invasion, as it was documented for woodchuck hepatitis virus (WHV) in the woodchuck model of hepatitis B (1 –3 ). The lack of validated cultures of normal human hepatocytes susceptible to hepatitis B virus (HBV) and capable of supporting efficient propagation of the virus in vitro had an adverse impact in the past and continues to hamper studies on HBV pathobiology, vaccine development, and preclinical evaluation of anti-HBV agents. A number of important issues, including delineation of the nature of HBV hepatotropism, the molecular basis of HBV persistence in the liver, the mechanisms of HBV oncogenesis, and the virus effect on hepatocyte survival and function, await elucidation in the appropriate culture models. The natural occurrence of viruses similar to HBV in some lower mammals provides an opportunity to establish hepatocyte cultures permissive to ortho -hepadnavirus infection and to circumvent, at least to some degree, problems posed by the absence of appropriate human hepatocyte cultures. Among mammalian hepadnaviruses, WHV infection in the eastern American woodchuck (Marmota monax ) has been validated as a valuable experimental paradigm of virologic, immunologic, and pathologic events occurring in HBV infection and hepatitis B in humans (3 –5 ).