THE C-TERMINUS OF THE HEPATITIS-B VIRUS-ANTIGEN PRECURSOR IS REQUIREDFOR A TUNICAMYCIN-SENSITIVE STEP THAT PROMOTES EFFICIENT SECRETION OFTHE ANTIGEN

The Hepatitis B virus encodes the secreted e antigen (HBe) whose funct ion in the viral life cycle is unknown. HBe derives from a 25-kDa prec ursor that is directed to the secretory pathway. After cleavage of the signal sequence, the resulting 22-kDa protein (P22) is processed in a post-endoplasmic reticulum compartment to mature HBe by removal of th e 34-amino acid C-terminal domain. The efficiency of HBe secretion is specifically decreased in cells grown in the presence of tunicamycin, an inhibitor of N-glycosylation, Inasmuch as HBe precursor is not N-gl ycosylated, our data suggest that a cellular tunicamycin-sensitive pro tein increases the intracellular transport through the HBe secretory p athway. The study of the secretion of HBe derived hom C-terminal-trunc ated precursors demonstrates that the tunicamycin sensitive secretion absolutely requires a part of the C-terminal region that is removed to form mature HBe, indicating that the cellular tunicamycin-sensitive p rotein increases the efficiency of the intracellular transport of P22. We have also shown that the Escherichia coli beta-galactosidase can b e secreted when fused to the HBe precursor signal sequence and that th e P22 C-terminal domain renders the secretion of this reporter protein also tunicamycin-sensitive.