title: Chondroitin sulfate characterized by the E-disaccharide unit is a potent inhibitor of herpes simplex virus infectivity and provides the virus binding sites on gro2C cells.
abstract: Although cell surface chondroitin sulfate (CS) is regarded as an auxiliary receptor for binding of herpes simplex virus to cells, and purified CS chain types A, B, and C are known to interfere poorly or not at all with the virus infection of cells, we have found that CS type E (CS-E), derived from squid cartilage, exhibited potent antiviral activity. The IC(50) values ranged from 0.06 to 0.2 mug/ml and substantially exceeded the antiviral potency of heparin, the known inhibitor of virus binding to cells. Furthermore, in mutant gro2C cells that express CS but not heparan sulfate, CS-E showed unusually high anti-herpes virus activity with IC(50) values of <1 ng/ml. Enzymatic degradation of CS-E with chondroitinase ABC abolished its antiviral activity. CS-E inhibited the binding to cells of the purified virus attachment protein gC. A direct interaction of gC with immobilized CS-E and inhibition of this binding by CS-E oligosaccharide fragments greater than octasaccharide were demonstrated. Likewise, the gro2C-specific CS chains interfered with the binding of viral gC to these cells and were found to contain a considerable proportion (13%) of the E-disaccharide unit, suggesting that this unit is an essential component of the CS receptor for herpes simplex virus on gro2C cells and that the antiviral activity of CS-E was due to interference with the binding of viral gC to a CS-E-like receptor on the cell surface. Knowledge of the determinants of antiviral properties of CS-E will help in the development of inhibitors of herpes simplex virus infections in humans.
authors: Department of Clinical Virology, Göteborg University, Sweden.
authors: Kicki
authors: K
authors: Bergefall
authors: Edward
authors: E
authors: Trybala
authors: Maria
authors: M
authors: Johansson
authors: Toru
authors: T
authors: Uyama
authors: Satomi
authors: S
authors: Naito
authors: Shuhei
authors: S
authors: Yamada
authors: Hiroshi
authors: H
authors: Kitagawa
authors: Kazuyuki
authors: K
authors: Sugahara
authors: Tomas
authors: T
authors: Bergström
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001665:Binding Sites; D002356:Cartilage / Q000378:metabolism; D002522:Chlorocebus aethiops; D019765:Chondroitin ABC Lyase / Q000737:chemistry; D002809:Chondroitin Sulfates / Q000737:chemistry*; D049832:Decapodiformes; D004187:Disaccharides / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006497:Heparan Sulfate / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D051379:Mice; D009844:Oligosaccharides / Q000737:chemistry; D011485:Protein Binding; D018139:Simplexvirus / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D019765:Chondroitin ABC Lyase; D002809:Chondroitin Sulfates; D004187:Disaccharides; D006497:Heparan Sulfate; D008024:Ligands; D009844:Oligosaccharides