title: Decay-accelerating factor binding determines the entry route of echovirus 11 in polarized epithelial cells.
abstract: The interaction between echovirus 11 strain 207 (EV11-207) and decay-accelerating factor (DAF or CD55) at the apical surface of polarized Caco-2 cells results in rapid transport of the virus to tight junctions and in its subsequent uptake. A virus mutant (EV11-207R) which differs at 6 amino acids and whose affinity for DAF is apparently significantly lower remains at the apical surface, from where its uptake occurs. Binding of EV11-207 to DAF and its transport to tight junctions result in a loss of function of the junctions. In contrast, the mutant virus EV11-207R is not transferred to tight junctions, nor does it impair the integrity of these junctions. Cholesterol depletion from the apical membrane leads to DAF aggregation and, presumably, internalization and inhibits infection by EV11-207. However, infection by EV11-207R is significantly less sensitive to cholesterol depletion than infection by EV11-207, confirming the DAF requirement for EV11-207, but not EV11-207R, to infect cells. These data strongly indicate that in the case of infection of polarized epithelial cells by echovirus 11, DAF binding appears be a key determinant in the choice of entry pathway, at least in cell culture.
authors.affiliation: Department of Clinical Pathology, University of Geneva, 1 Rue Michel Servet, 1211 Geneva 4, Switzerland. ks607@cam.ac.uk
authors.forename: Komla
authors.initials: K
authors.lastname: Sobo
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.forename: T David K
authors.initials: TD
authors.lastname: Brown
authors.forename: Amanda D
authors.initials: AD
authors.lastname: Stuart
authors.forename: Thomas A
authors.initials: TA
authors.lastname: McKee
mesh_terms: D018958:CD55 Antigens / Q000378:metabolism*; D018938:Caco-2 Cells; D016764:Cell Polarity; D002784:Cholesterol / Q000172:deficiency; D029822:Enterovirus B, Human / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000378:metabolism / Q000821:virology*; D004847:Epithelial Cells / Q000821:virology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D011485:Protein Binding; D019108:Tight Junctions / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D018958:CD55 Antigens; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol