Mucin-like region of herpes simplex virus type 1 attachment protein gC modulates the virus-glycosaminoglycan interaction.
Artikel i vetenskaplig tidskrift, 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

Författare

Noomi Altgärde

Chalmers, Teknisk fysik, Biologisk fysik

Charlotta Eriksson

Göteborgs universitet

Nadia Peerboom

Chalmers, Teknisk fysik, Biologisk fysik

Tuan Phan Xuan

Chalmers, Teknisk fysik, Kondenserade materiens fysik

SuMo Biomaterials

Stephanie Möller

Matthias Schnabelrauch

Sofia Svedhem

Chalmers, Teknisk fysik, Biologisk fysik

Edward Trybala

Göteborgs universitet

Tomas Bergström

Göteborgs universitet

Marta Bally

Chalmers, Teknisk fysik, Biologisk fysik

Journal of Biological Chemistry

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

Vol. 290 35 21473-21485

Ämneskategorier

Polymerkemi

Cellbiologi

Biokemi och molekylärbiologi

Medicinsk laboratorie- och mätteknik

Immunologi

Styrkeområden

Livsvetenskaper och teknik

Materialvetenskap

DOI

10.1074/jbc.M115.637363

PubMed

26160171

Mer information

Skapat

2017-10-07