title: Cardiovirulent coxsackieviruses and the decay-accelerating factor (CD55) receptor.
abstract: Group B coxsackieviruses are etiologically linked with many human diseases including acute myocarditis and associated chronic dilated cardiomyopathy. Well-established CVB3 cardiovirulent strains (CVB3c(s)) with known phenotypic difference have been used to study the pathogenesis of virus-induced heart disease. The receptor-binding characteristics of cardiovirulent CVB3 are not known, but may represent one mechanism accounting for differences in disease virulence. In this study, interactions between CVB3c(s) and the decay-accelerating factor (DAF or CD55) cell surface receptor were examined. Anti-DAF monoclonal antibodies (MAbs) blocked virus binding and infection of susceptible HeLa cells. Virus binding was significantly reduced by treatment of these cells with phosphatidylinositol phospholipase C enzyme, which rendered them DAF-deficient CVB3c(s) exhibited a differential propensity for the DAF receptor, as several cardiovirulent strains interacted more strongly than others. However, virus binding and infection was always most effectively blocked by MAbs directed against the SCR 2 and 3 domains of DAF, suggesting that binding occurs at a similar site(s) on the molecule for all strains. Virus binding and internalization were associated with DAF down-regulation at the cell surface, as monitored by flow cytometry analysis. Cardiovirulent CVB3 did not interact with molecules functionally and/or structurally related to DAF, including CD35, CD46, Factor H, or C4-binding protein. Adenovirus type 2 (Ad2) does not use the DAF receptor. However, competitive binding assays between Ad2 and CVB1-6, CVB3c(s), anti-DAF MAbs, or DAF-reduced cells indicated that DAF is associated with Ad2 receptors on the HeLa cell membrane. In summary, this study indicates that DAF is an attachment receptor for cardiovirulent CVB3 and that DAF interaction may be important in the pathogenesis of CVB-mediated heart disease.
authors.affiliation: Center for Cardiovascular Research, Toronto Hospital, Ontario, Canada.
authors.forename: T A
authors.initials: TA
authors.lastname: Martino
authors.forename: M
authors.initials: M
authors.lastname: Petric
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.forename: K
authors.initials: K
authors.lastname: Aitken
authors.forename: C J
authors.initials: CJ
authors.lastname: Gauntt
authors.forename: C D
authors.initials: CD
authors.lastname: Richardson
authors.forename: L H
authors.initials: LH
authors.lastname: Chow
authors.forename: P P
authors.initials: PP
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001667:Binding, Competitive; D018958:CD55 Antigens / Q000276:immunology / Q000502:physiology*; D002522:Chlorocebus aethiops; D003165:Complement System Proteins / Q000502:physiology; D003384:Coxsackievirus Infections / Q000209:etiology*; D029822:Enterovirus B, Human / Q000472:pathogenicity* / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009205:Myocarditis / Q000209:etiology*; D011991:Receptors, Virus / Q000502:physiology; D014709:Vero Cells; D014774:Virulence
chemical_list: D000911:Antibodies, Monoclonal; D018958:CD55 Antigens; D011991:Receptors, Virus; D003165:Complement System Proteins