title: Mucin-like Region of Herpes Simplex Virus Type 1 Attachment Protein Glycoprotein C (gC) Modulates the Virus-Glycosaminoglycan Interaction.
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.
authors.affiliation: From the Department of Applied Physics, Chalmers University of Technology, 412 96 Göteborg, Sweden.
authors.forename: Noomi
authors.initials: N
authors.lastname: Altgärde
authors.affiliation: the Department of Clinical Virology, University of Gothenburg, 413 46 Göteborg, Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Eriksson
authors.affiliation: From the Department of Applied Physics, Chalmers University of Technology, 412 96 Göteborg, Sweden.
authors.forename: Nadia
authors.initials: N
authors.lastname: Peerboom
authors.affiliation: From the Department of Applied Physics, Chalmers University of Technology, 412 96 Göteborg, Sweden.
authors.forename: Tuan
authors.initials: T
authors.lastname: Phan-Xuan
authors.affiliation: the Department of Biomaterials, INNOVENT e.V., Pruessingstrasse 27 B, D-07745 Jena, Germany, and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Moeller
authors.affiliation: the Department of Biomaterials, INNOVENT e.V., Pruessingstrasse 27 B, D-07745 Jena, Germany, and.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schnabelrauch
authors.affiliation: From the Department of Applied Physics, Chalmers University of Technology, 412 96 Göteborg, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Svedhem
authors.affiliation: the Department of Clinical Virology, University of Gothenburg, 413 46 Göteborg, Sweden.
authors.forename: Edward
authors.initials: E
authors.lastname: Trybala
authors.affiliation: the Department of Clinical Virology, University of Gothenburg, 413 46 Göteborg, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Bergström
authors.affiliation: 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.
authors.forename: Marta
authors.initials: M
authors.lastname: Bally
mesh_terms: D000818:Animals; D002460:Cell Line; D006025:Glycosaminoglycans / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D007700:Kinetics; D008856:Microscopy, Fluorescence; D009077:Mucins / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation; D009439:Neuraminidase / Q000378:metabolism; D009994:Osmolar Concentration; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism*; D014771:Virion / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D009077:Mucins; D050505:Mutant Proteins; D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1; D009439:Neuraminidase
keywords: carbohydrate-binding protein; glycoprotein; glycosaminoglycan; glycosylation; herpesvirus; mucin-like region; surface plasmon resonance (SPR)