Isolation and characterisation of potential respiratory syncytial virus receptor(s) on epithelial cells.
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.
Malhotra
Rajneesh
R
Respiratory and Inflammation CEDD, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. rm18326@gsk.com
Ward
Malcolm
M
Bright
Helen
H
Priest
Richard
R
Foster
Martyn R
MR
Hurle
Michael
M
Blair
Eddie
E
Bird
Michael
M
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
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