Glycobiology Advance Access originally published online on March 24, 2004
Glycobiology 2004 14(7):571-581; doi:10.1093/glycob/cwh075
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Glycobiology vol. 14 no. 7 © Oxford University Press 2004; all rights reserved.
Basic amino acids as modulators of an O-linked glycosylation signal of the herpes simplex virus type 1 glycoprotein gC: functional roles in viral infectivity
2 Department of Virology, University of Göteborg, Guldhedsgatan 10B; S-413 46 Göteborg, Sweden; and 3 Faculty of Health Sciences, School of Dentistry, Nørre Alle 20 DK-2200 N, Denmark
Received on September 22, 2003; revised on February 2, 2004; accepted on March 5, 2004
The herpes simplex virus type 1 (HSV-1) glycoprotein gC-1 is engaged both in viral attachment and viral immune evasion mechanisms in the infected host. Besides several N-linked glycans, gC-1 contains numerous O-linked glycans, mainly localized in two pronase-resistant clusters in the N-terminal domain of gC-1. In the present study we construct and characterize one gC-1 mutant virus, in which two basic amino acids (114K and 117R) in a putative O-glycosylation sequon were changed to alanine. We found that this modification did not modify the N-linked glycosylation but increased the content of O-linked glycans considerably. Analysis of the O-glycosylation capacity of wild-type and mutant gC-1 was performed by in vitro glycosylation assays with synthetic peptides derived from the mutant region predicted to present new O-glycosylation sites. Thus the mutant peptide region served as a better substrate for polypeptide GalNAc-transferase 2 than the wild-type peptide, resulting in increased rate and number of O-glycan attachment sites. The predicted increase in O-linked glycosylation resulted in two modifications of the biological properties of mutant virus—that is, an impaired binding to cells expressing chondroitin sulfate but not heparan sulfate on the cell surface and a significantly reduced plaque size in cultured cells. The results suggested that basic amino acids present within O-glycosylation signals may down-regulate the amount of O-linked glycans attached to a protein and that substitution of such amino acid residues may have functional consequences for a viral glycoprotein involving virus attachment to permissive cells as well as viral cell-to-cell spread.
1 To whom correspondence should be addressed; e-mail: sigvard.olofsson{at}microbio.gu.se
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