title: Antibody binding to individual short consensus repeats of decay-accelerating factor enhances enterovirus cell attachment and infectivity.
abstract: Decay-accelerating factor (DAF), a widely expressed membrane complement-regulatory protein, is utilized as a cellular receptor by many human enteric pathogens. We show here that the binding of two enteroviruses to individual short consensus repeats (SCR) of DAF on the cell surface is greatly augmented by mAb binding to an alternate SCR: Coxsackievirus A21 binding to the SCR1 of DAF is increased by Ab binding to SCR3 and, conversely, Echovirus 7 binding to SCR3 is enhanced severalfold by Ab binding to SCR1. These Ab-induced increases in viral binding also resulted in increased viral infectivity. Using purified soluble DAF in a solid phase assay it was found that Ab binding to SCR1 is increased greatly in the presence of an Ab against SCR3 and, reciprocally, Ab against SCR1 greatly increases Ab binding to SCR3. In contrast to the results obtained with the larger viral particles, however, this reciprocal Ab-induced enhancement of binding is not seen when measuring Ab binding to membrane-bound DAF SCR on the cell surface. These findings provide a possible explanation for functional differences between membrane-bound and soluble DAF with implications for a potential role for DAF-binding molecules in regulating DAF function. This is the first demonstration of enhancement of viral infectivity mediated by Ab against the viral receptor.
authors.affiliation: Department of Microbiology, Faculty of Medicine, The University of Newcastle, New South Wales, Australia. dshafren@mail.newcastle.edu.au
authors.forename: D R
authors.initials: DR
authors.lastname: Shafren
authors.forename: D J
authors.initials: DJ
authors.lastname: Dorahy
authors.forename: R F
authors.initials: RF
authors.lastname: Thorne
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.forename: R D
authors.initials: RD
authors.lastname: Barry
authors.forename: G F
authors.initials: GF
authors.lastname: Burns
mesh_terms: D000818:Animals; D001666:Binding Sites, Antibody; D018958:CD55 Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion; D002462:Cell Membrane / Q000276:immunology / Q000821:virology; D016384:Consensus Sequence / Q000276:immunology; D006224:Cricetinae; D004770:Enterovirus / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D029822:Enterovirus B, Human / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D011961:Receptors, Fc / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid / Q000276:immunology*; D012208:Rhabdomyosarcoma; D012995:Solubility; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology
chemical_list: D018958:CD55 Antigens; D011961:Receptors, Fc