COXSACKIEVIRUS A21 BINDS TO DECAY-ACCELERATING FACTOR BUT REQUIRES INTERCELLULAR-ADHESION MOLECULE-1 FOR CELL ENTRY

It is becoming increasingly apparent that many viruses employ multiple receptor molecules in their cell entry mechanisms, The human enterovi rus coxsackievirus A21 (CAV21) has been reported to bind to the N-term inal domain of intercellular adhesion molecule 1 (ICAM-1) and undergo limited replication in ICAM-1-expressing murine L cells. In this study , we show that in addition to binding to ICAM-1, CAV21 binds to the fi rst short consensus repeat (SCR) of decay-accelerating factor (DAF). D ual antibody blockade using both anti-ICAM-1 (domain 1) and anti-DAF ( SCR1) monoclonal antibodies (MAbs) is required to completely abolish b inding and replication of high-titered CAV21, However, the binding of CAV21 to DAF, unlike that to ICAM-1, does not initiate a productive ce ll infection. The capacity of an anti-DAF (SCR3) MAb to block CAV21 in fection but not binding, coupled with immunoprecipitation data from ch emical cross-linking studies, indicates that DAF and ICAM-1 are closel y associated on the cell surface, It is therefore suggested that DAF m ay function as a low-affinity attachment receptor either enhancing vir al presentation or providing a viral sequestration site for subsequent high-affinity binding to ICAM-1.