The C terminus of the hepatitis B virus e antigen precursor is required for a tunicamycin-sensitive step that promotes efficient secretion of the antigen.
The Hepatitis B virus encodes the secreted e antigen (HBe) whose function in the viral life cycle is unknown. HBe derives from a 25-kDa precursor 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 the 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-glycosylated, our data suggest that a cellular tunicamycin-sensitive protein increases the intracellular transport through the HBe secretory pathway. The study of the secretion of HBe derived from C-terminal-truncated 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 protein increases the efficiency of the intracellular transport of P22. We have also shown that the Escherichia coli beta-galactosidase can be secreted when fused to the HBe precursor signal sequence and that the P22 C-terminal domain renders the secretion of this reporter protein also tunicamycin-sensitive.
Messageot
F
F
Laboratoire de Génétique des Virus, Gif sur Yvette, France.
Carlier
D
D
Rossignol
J M
JM
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D006031:Glycosylation; D006513:Hepatitis B e Antigens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection; D014415:Tunicamycin / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000378:metabolism
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D011498:Protein Precursors; D014415:Tunicamycin; D001616:beta-Galactosidase