N-linked glycosylation of hepatitis B surface antigens is involved but not essential in the assembly of hepatitis delta virus.
Hepatitis delta virus (HDV) is a defective virus requiring the hepatitis B virus (HBV) to provide hepatitis B surface antigens as the envelope protein. The hepatitis B surface antigens are posttranslationally modified by N-linked glycosylation, and its significance in HDV assembly was investigated with a cotransfection system using human hepatoma cell line Huh-7. After the N-linked glycosylation of HBsAg was blocked by tunicamycin treatment, the packaging of HDV in the culture system could be suppressed to a level as low as 5-10% of the untreated control. The extent of inhibition correlated with the increased concentrations of tunicamycin. In contrast, the loss of HBsAg glycosylation did not affect the efficiency of assembly of HBV particles. When the N-linked glycosylation site of small HBsAg at amino acid 146 was mutated from asparagine to glutamine, the mutant HBsAg packaged only a modest amount of HDV particles. The quantity and kinetics of formation of HDV particles in culture system were reduced by the depletion of HBsAg glycosylation. Therefore HDV, similar to influenza and vesicular stomatitis viruses, depends on glycosylation of the envelope proteins as a signal for envelope protein maturation and for virion formation.
Wang
C J
CJ
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Sung
S Y
SY
Chen
D S
DS
Chen
P J
PJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D006031:Glycosylation; D018963:Hepatitis Antigens / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D003698:Hepatitis Delta Virus / Q000502:physiology*; D035923:Hepatitis delta Antigens; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000494:pharmacology; D019065:Virus Assembly / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D018963:Hepatitis Antigens; D006514:Hepatitis B Surface Antigens; D035923:Hepatitis delta Antigens; C442244:hepatitis delta virus large antigen; D014415:Tunicamycin