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J Biol Chem. 2015 Aug 28;290(35):21473-85. doi: 10.1074/jbc.M115.637363. Epub 2015 Jul 9.

Mucin-like Region of Herpes Simplex Virus Type 1 Attachment Protein Glycoprotein C (gC) Modulates the Virus-Glycosaminoglycan Interaction.

Author information

1
From the Department of Applied Physics, Chalmers University of Technology, 412 96 Göteborg, Sweden.
2
the Department of Clinical Virology, University of Gothenburg, 413 46 Göteborg, Sweden.
3
the Department of Biomaterials, INNOVENT e.V., Pruessingstrasse 27 B, D-07745 Jena, Germany, and.
4
From the Department of Applied Physics, Chalmers University of Technology, 412 96 Göteborg, Sweden, the Institut Curie, Centre de Recherche, CNRS, UMR 168, Physico-Chimie Curie, F-75248 Paris, France bally@chalmers.se.

Abstract

Glycoprotein C (gC) mediates the attachment of HSV-1 to susceptible host cells by interacting with glycosaminoglycans (GAGs) on the cell surface. gC contains a mucin-like region located near the GAG-binding site, which may affect the binding activity. Here, we address this issue by studying a HSV-1 mutant lacking the mucin-like domain in gC and the corresponding purified mutant protein (gCΔmuc) in cell culture and GAG-binding assays, respectively. The mutant virus exhibited two functional alterations as compared with native HSV-1 (i.e. decreased sensitivity to GAG-based inhibitors of virus attachment to cells and reduced release of viral particles from the surface of infected cells). Kinetic and equilibrium binding characteristics of purified gC were assessed using surface plasmon resonance-based sensing together with a surface platform consisting of end-on immobilized GAGs. Both native gC and gCΔmuc bound via the expected binding region to chondroitin sulfate and sulfated hyaluronan but not to the non-sulfated hyaluronan, confirming binding specificity. In contrast to native gC, gCΔmuc exhibited a decreased affinity for GAGs and a slower dissociation, indicating that once formed, the gCΔmuc-GAG complex is more stable. It was also found that a larger number of gCΔmuc bound to a single GAG chain, compared with native gC. Taken together, our data suggest that the mucin-like region of HSV-1 gC is involved in the modulation of the GAG-binding activity, a feature of importance both for unrestricted virus entry into the cells and release of newly produced viral particles from infected cells.

KEYWORDS:

carbohydrate-binding protein; glycoprotein; glycosaminoglycan; glycosylation; herpesvirus; mucin-like region; surface plasmon resonance (SPR)

PMID:
26160171
PMCID:
PMC4571874
DOI:
10.1074/jbc.M115.637363
[Indexed for MEDLINE]
Free PMC Article

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