Hepatitis B virus MHBs antigen is selectively sensitive to glucosidase-mediated processing in the endoplasmic reticulum

Previous studies have shown that hepatitis B virus (HBV) secretion from Hep G 2.2.15 cells is prevented by inhibitors of the endoplasmic reticulum (ER) glucosidase under conditions where secretion of cellular glycoproteins are not detectably affected. The 2.2.15 cells are derived from HepG2 and conta in intact dimers of the viral genome. They produce and secrete infectious H BV. The secretion of the viral envelope polypeptide, MHBs, was selectively and quantitatively reduced from 2.2.15 cells in which glucosidase was inhib ited, whereas the envelope polypeptide, SHBs, was relatively insensitive, b eing as resistant as were most host glycoproteins. Because 2.2.15 cells exp ress all HBV ORFs, it seemed possible that the sensitivity of MHBs secretio n involved its interaction with the viral nucleocapsid or other viral gene products. The work reported here showed that MHBs secretion from HepG2 cell s transfected with a plasmid that expresses only the MHBs polypeptide was a s sensitive to glucosidase inhibitors as it was from 2.2.15 cells. These da ta show that the sensitivity of the MHBs polypeptide secretion to glucosida se inhibitors is entirely encrypted within its structural gene. The reasons the MHBs polypeptide, but not SHBs, is so sensitive to glucosidase process ing are discussed.