Nuclear antigen detected in hepatoma cell lines containing integrated hepatitis B virus DNA

We identified, by anticomplement immunofluorescence, a nuclear antigen (hepatitis B virus-associated nuclear antigen [HBNA]) in two human hepatoma cell lines containing integrated hepatitis B virus DNA but not in three hepatoma cell lines lacking it. The antigen resembled neoantigens associated with the oncogenesis of certain papovaviruses, adenoviruses, and herpesviruses. Antibody to the antigen (anti-HBNA) was found in 7.3% of hepatitis B surface antigen-positive sera from patients with hepatocellular carcinoma but not in surface antigen-negative sera. The staining of HBNA was characterized by two patterns, reticular nuclear fluorescence and nucleolar fluorescence. The expression of HBNA did not parallel the production of extracellular hepatitis B surface antigen. Treatment of cells with proteinase K, RNase, DNase, or cycloheximide significantly diminished the staining of HBNA.