title: Sulfated homologues of heparin inhibit hepatitis C virus entry into mammalian cells.
abstract: The mechanism of entry of hepatitis C virus (HCV) through interactions between the envelope glycoproteins and specific cell surface receptors remains unclear at this time. We have previously shown with the vesicular stomatitis virus (VSV)/HCV pseudotype model that the hypervariable region 1 of the HCV E2 envelope glycoprotein helps in binding with glycosaminoglycans present on the cell surface. In this study, we have examined the binding of HCV envelope glycoproteins with chemically modified derivatives of heparin. Furthermore, we have determined the functional relevance of the interaction of heparin derivatives with HCV envelope glycoproteins for infectivity by using a human immunodeficiency virus (HIV)/HCV pseudotype, a VSV/HCV pseudotype, and cell culture-grown HCV genotype 1a. Taken together, our results suggest that the HCV envelope glycoproteins rely upon O-sulfated esters of a heparin homologue to facilitate entry into mammalian cells.
authors.affiliation: Division of Infectious Diseases & Immunology, Department of Internal Medicine, Saint Louis University, 3635 Vista Ave., FDT-8N, St. Louis, MO 63110, USA.
authors.forename: Arnab
authors.initials: A
authors.lastname: Basu
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Aster
authors.initials: A
authors.lastname: Beyene
authors.forename: Kousuke
authors.initials: K
authors.lastname: Saito
authors.forename: Keith
authors.initials: K
authors.lastname: Meyer
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ray
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002477:Cells; D015686:Gene Products, env / Q000378:metabolism; D006678:HIV / Q000235:genetics / Q000254:growth & development; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006493:Heparin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D011485:Protein Binding; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000254:growth & development; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D015686:Gene Products, env; D006493:Heparin