title: The fusion glycoprotein of human respiratory syncytial virus facilitates virus attachment and infectivity via an interaction with cellular heparan sulfate.
abstract: Human respiratory syncytial virus (RSV) F glycoprotein (RSV-F) can independently interact with immobilized heparin and facilitate both attachment to and infection of cells via an interaction with cellular heparan sulfate. RSV-glycosaminoglycan (GAG) interactions were evaluated using heparin-agarose affinity chromatography. RSV-F from A2- and B1/cp-52 (cp-52)-infected cell lysates, RSV-F derived from a recombinant vaccinia virus, and affinity-purified F protein all bound to and were specifically eluted from heparin columns. In infectivity inhibition studies, soluble GAGs decreased the infectivity of RSV A2 and cp-52, with bovine lung heparin exhibiting the highest specific activity against both A2 (50% effective dose [ED(50)] = 0.28 +/- 0.11 microg/ml) and cp-52 (ED(50) = 0.55 +/- 0. 14 microg/ml). Furthermore, enzymatic digestion of cell surface GAGs by heparin lyase I and heparin lyase III but not chondroitinase ABC resulted in a significant reduction in cp-52 infectivity. Moreover, bovine lung heparin inhibited radiolabeled A2 and cp-52 virus binding up to 90%. Taken together, these data suggest that RSV-F independently interacts with heparin/heparan sulfate and this type of interaction facilitates virus attachment and infectivity.
authors.affiliation: Laboratory of Pediatric and Respiratory Virus Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20852-1448, USA. feldmans@cber.fda.gov
authors.forename: S A
authors.initials: SA
authors.lastname: Feldman
authors.forename: S
authors.initials: S
authors.lastname: Audet
authors.forename: J A
authors.initials: JA
authors.lastname: Beeler
mesh_terms: D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D002522:Chlorocebus aethiops; D019765:Chondroitin ABC Lyase / Q000378:metabolism; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D006025:Glycosaminoglycans / Q000494:pharmacology; D015707:HN Protein; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D019763:Heparin Lyase / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D018113:Respiratory Syncytial Virus, Human / Q000378:metabolism* / Q000472:pathogenicity; D014709:Vero Cells; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins / Q000378:metabolism* / Q000502:physiology; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000378:metabolism* / Q000502:physiology
chemical_list: D019765:Chondroitin ABC Lyase; D006025:Glycosaminoglycans; D015707:HN Protein; D006493:Heparin; D019763:Heparin Lyase; D006497:Heparan Sulfate; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C116204:attachment protein G