Electron and Immunoelectron Microscopic Study of Dane Particle Formation in Chronic Hepatitis B Virus Infection

The site of Dane particle formation in hepatocytes was studied by routine electron and immunoelectron microscopy of liver biopsy specimens from 10 patients with hepatitis B e antigen-positive chronic active hepatitis. With routine electron microscopy, core particles were abundant in cytosol, often adjacent to the cell membrane, and occasionally in the microvilli. Figures suggestive of budding of endoplasmic reticulum with a core particle into the cisternae of endoplasmic reticulum were observed frequently. There were also figures suggestive of direct budding with a core particle from the surface of the cell. With the immunoelectron microscopy, the core particles were found to be positive for hepatitis B core antigen and the endoplasmic reticulum and the plasma membrane were positive for hepatitis B surface antigen. These findings suggest that the most plausible mode of formation of the Dane particle is by budding of hepatitis B surface antigen-positive endoplasmic reticulum membrane into the cisternae. In addition, formation of the Dane particle may also take place at the surface of the hepatocyte by a similar mechanism.