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 HepG 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 contain intact dimers of the viral genome. They produce and secrete infectious HBV. The secretion of the viral envelope polypeptide, MHBs, was selectively and quantitatively reduced from 2.2.15 cells in which glucosidase was inhibited, whereas the envelope polypeptide, SHBs, was relatively insensitive, being as resistant as were most host glycoproteins. Because 2.2.15 cells express all HBV ORFs, it seemed possible that the sensitivity of MHBs secretion involved its interaction with the viral nucleocapsid or other viral gene products. The work reported here showed that MHBs secretion from HepG2 cells transfected with a plasmid that expresses only the MHBs polypeptide was as sensitive to glucosidase inhibitors as it was from 2.2.15 cells. These data show that the sensitivity of the MHBs polypeptide secretion to glucosidase inhibitors is entirely encrypted within its structural gene. The reasons the MHBs polypeptide, but not SHBs, is so sensitive to glucosidase processing are discussed.
Lu
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X
Department of Biochemistry and Molecular Pharmacology, The Jefferson Center of Thomas Jefferson University, Doylestown, Pennsylvania, USA.
Lu
Y
Y
Geschwindt
R
R
Dwek
R A
RA
Block
T M
TM
D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000821:virology*; D005814:Genes, Viral; D005959:Glucosidases / Q000378:metabolism*; D006031:Glycosylation; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D011499:Protein Processing, Post-Translational; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000235:genetics
D006514:Hepatitis B Surface Antigens; D014759:Viral Envelope Proteins; D015678:Viral Structural Proteins; C114312:middle envelope protein, Hepatitis B virus; D005959:Glucosidases