ECHOVIRUS-1 INTERACTION WITH THE HUMAN VERY LATE ANTIGEN-2 (INTEGRIN-ALPHA-2-BETA-1) I-DOMAIN - IDENTIFICATION OF 2 INDEPENDENT VIRUS CONTACT SITES DISTINCT FROM THE METAL, ION-DEPENDENT ADHESION SITE

The human integrin very late antigen (VLA)-2 (CD49b/CD29) mediates int eractions with collagen and is the receptor for echovirus 1. Binding s ites for both collagen and echovirus 1 have been mapped to the I domai n within the alpha 2 subunit of the VLA-2 alpha 2 beta 1 heterodimer. Although murine VLA-2 interacts with collagen, it does not bind virus. We have used isolated human-murine chimeric I domains expressed as gl utathione S-transferase fusion proteins in Escherichia coli to identif y two groups of amino acids, 199-201 and 212-216, independently involv ed in virus attachment. These residues are distinct from the metal ion -dependent adhesion site previously demonstrated to be essential for V LA-2 interactions with collagen. Mutations in three metal ion-dependen t adhesion site residues that abolish adhesion to collagen had no effe ct on virus binding. These results confirm that different sites within the I domain are responsible for VLA-2 interaction with extracellular matrix proteins and with viral ligands.