Mucin-like region of herpes simplex virus type 1 attachment protein gC modulates the virus-glycosaminoglycan interaction.
Journal article, 2015

Glycoprotein C (gC) mediates the attachment of herpes simplex virus type 1 (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 an 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 to 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 to 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.

Herpesvirus

mucin-like region

surface plasmon resonance (SPR)

glycosaminoglycan

glycoprotein

carbohydrate-binding protein

glycosylation

Author

Noomi Altgärde

Chalmers, Applied Physics, Biological Physics

Charlotta Eriksson

University of Gothenburg

Nadia Peerboom

Chalmers, Applied Physics, Biological Physics

Tuan Phan Xuan

Chalmers, Applied Physics, Condensed Matter Physics

SuMo Biomaterials

Stephanie Möller

Matthias Schnabelrauch

Sofia Svedhem

Chalmers, Applied Physics, Biological Physics

Edward Trybala

University of Gothenburg

Tomas Bergström

University of Gothenburg

Marta Bally

Chalmers, Applied Physics, Biological Physics

Journal of Biological Chemistry

0021-9258 (ISSN) 1083-351X (eISSN)

Vol. 290 35 21473-21485

Subject Categories

Polymer Chemistry

Cell Biology

Biochemistry and Molecular Biology

Medical Laboratory and Measurements Technologies

Immunology

Areas of Advance

Life Science Engineering (2010-2018)

Materials Science

DOI

10.1074/jbc.M115.637363

PubMed

26160171

More information

Created

10/7/2017