Cytoplasmic interactions between decay-accelerating factor and intercellular adhesion molecule-1 are not required for coxsackievirus A21 cell infection

Picornaviral Research Unit, Discipline of Immunology and Microbiology and 2 Cancer Research Unit, Faculty of Medicine and Health Sciences, The University of Newcastle, Level 3, David Maddison Clinical Sciences Building, Royal Newcastle Hospital, Newcastle, 2300 New South Wales, Australia Author for correspondence: Darren Shafren. Fax +61 2 4923 6814. e-mail dshafren{at}mail.newcastle.edu.au Coxsackievirus A21 (CAV-21) employs a cell receptor complex of decay-accelerating factor (DAF) and intercellular adhesion molecule-1 (ICAM-1) for cell infectivity. In this study, the nature of potential extra- and/or intracellular interactions between DAF and ICAM-1 involved in picornaviral cell entry was investigated. Firstly, it was shown that intracellular interplay between DAF and ICAM-1 is not required for CAV-21 infection, as CAV-21 lytic infection mediated via the DAF/ICAM-1 receptor complex is not inhibited by replacement of the transmembrane and cytoplasmic domains of ICAM-1 with those from an unrelated cell surface molecule, CD36. By immunoprecipitation, chemical cross-linking and picornaviral binding assays, the existence of a close spatial association between DAF and ICAM-1 on the surface of ICAM-1-transfected RD cells was confirmed. Furthermore, it was shown that potential extracellular DAF/ICAM-1 interactions are likely to occur in an area on or proximal to DAF SCR3 and may influence the route of CAV-21 cell entry.