A DECAY-ACCELERATING FACTOR-BINDING STRAIN OF COXSACKIEVIRUS B3 REQUIRES THE COXSACKIEVIRUS-ADENOVIRUS RECEPTOR PROTEIN TO MEDIATE LYTIC INFECTION OF RHABDOMYOSARCOMA CELLS

The composition of the cellular receptor complex for coxsackievirus B3 (CVB3) has been an area of much contention for the last 30 years, Rec ently, two individual components of a putative CVB3 cellular receptor complex have been identified as (i) decay-accelerating factor (DAF) an d (ii) the coxsackievirus-adenovirus receptor protein (CAR), The prese nt study elucidates the individual roles of DAF and CAR in cell entry of CVB3 Nancy, First, we confirm that the DAF-binding phenotype of CVB 3 correlates to the presence of key amino acids located in the viral c apsid protein, VP2. Second, using antibody blockade, we show that comp lete protection of permissive cells from infection by high input multi plicities of CVB3 requires a combination of both anti-DAF and anti-CAR antibodies, Finally, it is shown that expression of the CAR protein o n the surface of nonpermissive DAF-expressing RD cells renders them hi ghly susceptible to CVB3-mediated lytic infection, Therefore, although the majority of CVB3 Nancy attaches to the cell via DAF, only virus d irectly interacting with the CAR protein mediates lytic infection, The role of DAF in CVB3 cell infection may be analogous to that recently described for coxsackievirus A21 (D. R. Shafren, D. J. Dorahy, R. A. I ngham, G. F. Burns, and R. D. Barry, J. Virol. 71:4736-4743, 1997), in that DAF may act as a CVB3 sequestration site, enhancing viral presen tation to the functional CAR protein.