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 enterovirus coxsackievirus A21 (CAV21) has been reported to bind to the N-terminal 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 first short consensus repeat (SCR) of decay-accelerating factor (DAF). Dual antibody blockade using both anti-ICAM-1 (domain 1) and anti-DAF (SCR1) monoclonal antibodies (MAbs) is required to completely abolish binding and replication of high-titered CAV21. However, the binding of CAV21 to DAF, unlike that to ICAM-1, does not initiate a productive cell infection. The capacity of an anti-DAF (SCR3) MAb to block CAV21 infection but not binding, coupled with immunoprecipitation data from chemical cross-linking studies, indicates that DAF and ICAM-1 are closely associated on the cell surface. It is therefore suggested that DAF may function as a low-affinity attachment receptor either enhancing viral presentation or providing a viral sequestration site for subsequent high-affinity binding to ICAM-1.
Shafren
D R
DR
Department of Microbiology, Faculty of Medicine, The University of Newcastle, New South Wales, Australia. dshafren@medicine-dmb.newcastle.ed.au
Dorahy
D J
DJ
Ingham
R A
RA
Burns
G F
GF
Barry
R D
RD
D000818:Animals; D001665:Binding Sites; D018958:CD55 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion; D003384:Coxsackievirus Infections / Q000382:microbiology; D006224:Cricetinae; D004770:Enterovirus / Q000254:growth & development*; D006367:HeLa Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins; D012091:Repetitive Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured
D018958:CD55 Antigens; D011991:Receptors, Virus; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase