title: Novel role for decay-accelerating factor in coxsackievirus A21-mediated cell infectivity.
abstract: Decay-accelerating factor (DAF) is involved in the cell membrane attachment of many human enteroviruses. Presently, further specific active roles of DAF in mediating productive cell infection and in the pathogenesis of natural enterovirus infection are poorly understood. In an attempt to more fully understand the role of DAF in lytic cell infection we examined the specific interactions of the prototype strain of coxsackievirus A21 (CVA21) with surface-expressed DAF. Investigations into discrete DAF-CVA21 interactions focused on viral binding; viral particle elution with respect to the parameters of time, temperature, and pH; and subsequent cell infection. Radiolabeled-virus binding assays revealed that peak elution of CVA21 from DAF occurred within 15 min of initial attachment and that the DAF-eluted virus increased in a linear fashion with respect to temperature and pH. CVA21 eluted from endogenous surface-expressed DAF was highly infectious, in contrast to CVA21 eluted from intercellular adhesion molecule 1 (ICAM-1), which retained little to no infectivity. Using an adenovirus transduction system, we demonstrate that CVA21 can remain infectious for up to 24 h after DAF binding and is capable of initiating a multicycle lytic infection upon delayed ICAM-1 surface expression. Taken together, the data suggest that a major role of DAF in cell infection by the prototype strain of CVA21 is to provide membrane concentration of infectious virions, effectively increasing viral interactions with endogenous or induced ICAM-1.
authors.affiliation: The Picornaviral Research Unit, Discipline of Immunology and Microbiology, Faculty of Health, The University of Newcastle, Level 3, David Maddison Clinical Sciences Building, Royal Newcastle Hospital, Newcastle, New South Wales 2300, Australia.
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Newcombe
authors.forename: Leone G
authors.initials: LG
authors.lastname: Beagley
authors.forename: Dale
authors.initials: D
authors.lastname: Christiansen
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Loveland
authors.forename: E Susanne
authors.initials: ES
authors.lastname: Johansson
authors.forename: Ken W
authors.initials: KW
authors.lastname: Beagley
authors.forename: Richard D
authors.initials: RD
authors.lastname: Barry
authors.forename: Darren R
authors.initials: DR
authors.lastname: Shafren
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D004770:Enterovirus / Q000472:pathogenicity*; D006863:Hydrogen-Ion Concentration; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology
chemical_list: D018958:CD55 Antigens; D018799:Intercellular Adhesion Molecule-1