Journal
JOURNAL OF VIROLOGY
Volume 80, Issue 19, Pages 9798-9810Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00577-06
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Funding
- Medical Research Council [G0500365] Funding Source: Medline
- MRC [G0500365] Funding Source: UKRI
- Medical Research Council [G0500365] Funding Source: researchfish
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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 alpha v beta 6 or alpha v beta 8 but not for inhibition of virus binding to alpha v beta 3. 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 alpha v beta 6. In contrast, although RGDM-containing peptides were effective for alpha v beta 8, RGDR-containing peptides were not. These observations were confirmed by showing that a virus containing an RGDR motif uses alpha v beta 8 less efficiently than alpha v beta 6 as a receptor for infection. Finally, evidence is presented that shows alpha v beta 3 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 alpha v beta 6 with a higher affinity than to alpha v beta 3 and alpha v beta 8.
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