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ABSTRACT Foot-and-mouth disease virus (FMDV) can use a number of integrins as receptors to initiate infection. Attachment to the integrin is mediated by a highly conserved arginine-glycine-aspartic acid (RGD) tripeptide located on the GH loop of VP1. Other residues of this loop are also conserved and may contribute to integrin binding. In this study we have used a 17-mer peptide, whose sequence corresponds to the GH loop of VP1 of type O FMDV, as a competitor of integrin-mediated virus binding and infection. Alanine substitution through this peptide identified the leucines at the first and fourth positions following RGD (RGD+1 and RGD+4 sites) as key for inhibition of virus binding and infection mediated by αvβ6 or αvβ8 but not for inhibition of virus binding to αvβ3. We also show that FMDV peptides containing either methionine or arginine at the RGD+1 site, which reflects the natural sequence variation seen across the FMDV serotypes, are effective inhibitors for αvβ6. In contrast, although RGDM-containing peptides were effective for αvβ8, RGDR-containing peptides were not. These observations were confirmed by showing that a virus containing an RGDR motif uses αvβ8 less efficiently than αvβ6 as a receptor for infection. Finally, evidence is presented that shows αvβ3 to be a poor receptor for infection by type O FMDV. Taken together, our data suggest that the integrin binding loop of FMDV has most likely evolved for binding to αvβ6 with a higher affinity than to αvβ3 and αvβ8.

Original publication

DOI

10.1128/jvi.00577-06

Type

Journal article

Journal

Journal of Virology

Publisher

American Society for Microbiology

Publication Date

10/2006

Volume

80

Pages

9798 - 9810