Intrahepatic expression of HBcAg in chronic HBV hepatitis: Lessons from molecular biology

The precore and core proteins of hepatitis B virus have identical deduced amino acid sequences other than a 29‐residue amino‐terminal extension (precore region) on the precore protein. The first 19 of these residues serve as a signal sequence to direct the precore protein to the endoplasmic reticulum, where they are cleaved off with formation of precore protein derivative P22 for secretion. In this report, we show that P22 can alternatively be transported into the nucleus following signal peptide cleavage. Experiments with deletion mutants indicated that this nuclear transport proceeds via the cytosol and is dependent on the amino‐terminal portion of P22. Thus, the hepatitis B virus precore protein is a secreted, cytosolic, and nuclear protein.