title: Coxsackievirus A21 binds to decay-accelerating factor but requires intercellular adhesion molecule 1 for cell entry.
abstract: It is becoming increasingly apparent that many viruses employ multiple receptor molecules in their cell entry mechanisms. The human enterovirus coxsackievirus A21 (CAV21) has been reported to bind to the N-terminal domain of intercellular adhesion molecule 1 (ICAM-1) and undergo limited replication in ICAM-1-expressing murine L cells. In this study, we show that in addition to binding to ICAM-1, CAV21 binds to the first short consensus repeat (SCR) of decay-accelerating factor (DAF). Dual antibody blockade using both anti-ICAM-1 (domain 1) and anti-DAF (SCR1) monoclonal antibodies (MAbs) is required to completely abolish binding and replication of high-titered CAV21. However, the binding of CAV21 to DAF, unlike that to ICAM-1, does not initiate a productive cell infection. The capacity of an anti-DAF (SCR3) MAb to block CAV21 infection but not binding, coupled with immunoprecipitation data from chemical cross-linking studies, indicates that DAF and ICAM-1 are closely associated on the cell surface. It is therefore suggested that DAF may function as a low-affinity attachment receptor either enhancing viral presentation or providing a viral sequestration site for subsequent high-affinity binding to ICAM-1.
authors.affiliation: Department of Microbiology, Faculty of Medicine, The University of Newcastle, New South Wales, Australia. dshafren@medicine-dmb.newcastle.ed.au
authors.forename: D R
authors.initials: DR
authors.lastname: Shafren
authors.forename: D J
authors.initials: DJ
authors.lastname: Dorahy
authors.forename: R A
authors.initials: RA
authors.lastname: Ingham
authors.forename: G F
authors.initials: GF
authors.lastname: Burns
authors.forename: R D
authors.initials: RD
authors.lastname: Barry
mesh_terms: D000818:Animals; D001665:Binding Sites; D018958:CD55 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion; D003384:Coxsackievirus Infections / Q000382:microbiology; D006224:Cricetinae; D004770:Enterovirus / Q000254:growth & development*; D006367:HeLa Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins; D012091:Repetitive Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured
chemical_list: D018958:CD55 Antigens; D011991:Receptors, Virus; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase