title: Isolation and characterisation of potential respiratory syncytial virus receptor(s) on epithelial cells.
abstract: Respiratory syncytial virus (RSV) infection causes severe lower respiratory diseases in infancy, early childhood and the elderly. RSV infections respond poorly to current therapies. Therefore, we initiated a search for novel drug targets by investigating the characteristics and identity of RSV adhesion receptors on mammalian cells. Soluble human lectins, complex polysaccharides and a low molecular selectin antagonist, TBC1269, were used to characterise and isolate the RSV receptor on a human epithelial cell line (Hep2 cells). The binding characteristics of the RSV receptor on Hep2 cells were similar to those reported for L-selectin. The carbohydrate-based selectin antagonists, fucoidan and TBC 1269, inhibit RSV infection both in vitro and in a mouse model of infection. Furthermore, we have isolated annexin II as a potential RSV receptor on Hep2 cells. The expression of annexin II was increased after RSV infection. Recombinant annexin II binds to RSV G-protein, heparin and plasminogen and the binding is inhibited by a selectin antagonist, TBC1269. These findings indicate that inhibitors of annexin II could have potential in treating RSV infection.
authors.affiliation: Respiratory and Inflammation CEDD, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. rm18326@gsk.com
authors.forename: Rajneesh
authors.initials: R
authors.lastname: Malhotra
authors.forename: Malcolm
authors.initials: M
authors.lastname: Ward
authors.forename: Helen
authors.initials: H
authors.lastname: Bright
authors.forename: Richard
authors.initials: R
authors.lastname: Priest
authors.forename: Martyn R
authors.initials: MR
authors.lastname: Foster
authors.forename: Michael
authors.initials: M
authors.lastname: Hurle
authors.forename: Eddie
authors.initials: E
authors.lastname: Blair
authors.forename: Michael
authors.initials: M
authors.lastname: Bird
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D019041:L-Selectin / Q000187:drug effects / Q000378:metabolism; D008358:Mannose / Q000031:analogs & derivatives; D008362:Mannosides / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use; D011991:Receptors, Virus / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000378:metabolism / Q000472:pathogenicity*; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D017306:Annexin A2; D001713:Biphenyl Compounds; D008362:Mannosides; D011134:Polysaccharides; D011991:Receptors, Virus; D014764:Viral Proteins; D019041:L-Selectin; C108700:bimosiamose disodium; C007789:fucoidan; D008358:Mannose