Hepatitis B virus (HBV) envelope glycoproteins vary drastically in their sensitivity to glycan processing: evidence that alteration of a single N-linked glycosylation site can regulate HBV secretion.
The role of N-linked glycosylation and glycan trimming in the function of glycoproteins remains a central question in biology. Hepatitis B virus specifies three glycoproteins (L, M, and S) that are derived from alternate translation of the same ORF. All three glycoproteins contain a common N-glycosylation site in the S domain while M possesses an additional N-glycosylation site at its amino terminus. In the presence of N-butyl-deoxnojirimycin (an inhibitor of alpha-glucosidase) virions and the M protein are surprisingly retained. Preliminary evidence suggests that the retained M protein is hyperglucosylated and localized to lysosomal vesicles. In contrast, the S and L proteins are secreted, and their glycosylation state is unaffected by the presence of the inhibitor. Site-directed mutagenesis provides evidence that virion secretion requires the glycosylation sequon in the pre-S2 domain of M. This highlights the potential role of the M protein oligosaccharide as a therapeutic target.
Mehta
A
A
The Glycobiology Institute, Department of Biochemistry, Oxford University, United Kingdom.
Lu
X
X
Block
T M
TM
Blumberg
B S
BS
Dwek
R A
RA
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000494:pharmacology; D000954:Antigens, Surface / Q000032:analysis; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular; D002499:Centrifugation, Density Gradient; D004279:DNA, Viral / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D006031:Glycosylation; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000378:metabolism*
D000954:Antigens, Surface; D004279:DNA, Viral; D065089:Glycoside Hydrolase Inhibitors; C096362:L protein, hepatitis B virus; D009844:Oligosaccharides; D011134:Polysaccharides; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D017485:1-Deoxynojirimycin