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Journal of Virology, October 2006, p. 9798-9810, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00577-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Specificity of the VP1 GH Loop of Foot-and-Mouth Disease Virus for {alpha}v Integrins

Alison Burman,1 Stuart Clark,1 Nicola G. A. Abrescia,2 Elizabeth E. Fry,2 David I. Stuart,2 and Terry Jackson1*

Division of Microbiology, Institute for Animal Health, Pirbright, Surrey, GU24 ONF, United Kingdom,1 Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom2

Received 21 March 2006/ Accepted 18 July 2006

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}vß6 or {alpha}vß8 but not for inhibition of virus binding to {alpha}vß3. 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}vß6. In contrast, although RGDM-containing peptides were effective for {alpha}vß8, RGDR-containing peptides were not. These observations were confirmed by showing that a virus containing an RGDR motif uses {alpha}vß8 less efficiently than {alpha}vß6 as a receptor for infection. Finally, evidence is presented that shows {alpha}vß3 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}vß6 with a higher affinity than to {alpha}vß3 and {alpha}vß8.

* Corresponding author. Mailing address: Pirbright Laboratory, Institute for Animal Health, Ash Road, Pirbright, Surrey GU24 ONF, United Kingdom. Phone: 44 1483-232441. Fax: 44 1483-232448. E-mail: terry.jackson{at}bbsrc.ac.uk.

Journal of Virology, October 2006, p. 9798-9810, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00577-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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