CHARACTERIZATION AND BIOSYNTHESIS OF THE WOODCHUCK HEPATITIS-VIRUS E-ANTIGEN

The biosynthesis of the secretory core gene product of the woodchuck h epatitis virus (WHV) was studied in human cells. We have shown that th e WHV e antigen was a N-glycosylated (most likely a diglycosylated) pr otein, with an apparent M(r) of 24K. To demonstrate that the WHV preco re protein was correctly processed in human cells, we engineered chime ric proteins in which signal peptides or arginine-rich domains of WHV and hepatitis B virus (HBV) precore proteins were exchanged. Our resul ts showed that both the signal peptide and the arginine-rich region of WHV precore protein were cleaved off during the secretion pathway, as previously reported for precore protein of human HBV and duck HBV. Th ese observations demonstrate that the maturation process of the e anti gen is conserved in hepadnaviruses. In addition, on the basis of inhib ition experiments, we suggest that the cleavage of the carboxy terminu s of the WHV precore protein occurred in a post-endoplasmic reticulum compartment, most likely beyond the medial Golgi, and that this cleava ge was catalysed by an aspartyl protease.