Hepatitis B virus core antigen (HBc Ag) accumulation in an HBV nonproducer clone of HepG2-transfected cells is associated with cytopathic effect

Abstract

Two clones of the hepatoblastoma HepG2 cell line transfected with complete hepatitis B virus deoxyribonucleic acid (HBV DNA) were studied. The kinetics and cytopathic effect of HBV Ag production in these two clones (one of which was an HBV producer) were compared to those of the parent HepG2 cell line. The presence of hepatitis B surface antigen (HBs Ag) and hepatitis B e antigen (HBe Ag) was determined by commercial enzyme-linked immunosorbent assay (ELISA). A hepatitis B core antigen (HBc Ag)-specific ELISA assay was developed, using monoclonal anti-HBc to detect HBc Ag. Amounts of HBs, HBe, and HBc Ags were partially quantified in both intracellular and extracellular compartments. The HBV producer clone excreted high levels of HBc, HBe, and HBs Ags from the beginning of the growth phase, and no cytopathic effect was observed. The HBV nonproducer clone produced high levels of HBs and HBe Ags, but there was no detectable HBc Ag in the supernatant; instead, HBc Ag accumulated in the intracellular compartment. In this clone, significant cell death was observed 4 days after cell confluency, corresponding with notable HBc Ag release into the supernatant. These results suggest a cytopathic effect associated with HBc Ag accumulation in the HBV nonproducer clone, but no cytopathic effect in the HBV producer clone. This suggests that virological factors as well as the host's immune response may be considered in explaining liver injury occurring in hepatitis B.