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Journal of Virology, February 2008, p. 1537-1546, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01480-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Foot-and-Mouth Disease Virus Forms a Highly Stable, EDTA-Resistant Complex with Its Principal Receptor, Integrin {alpha}vβ6: Implications for Infectiousness{triangledown}

Danielle DiCara,1,{ddagger} Alison Burman,2,{ddagger} Stuart Clark,2 Stephen Berryman,2 Mark J. Howard,3 Ian R. Hart,1 John F. Marshall,1,{dagger}* and Terry Jackson2,{dagger}*

Institute of Cancer, Centre for Tumour Biology, Barts and the London Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, United Kingdom,1 Division of Microbiology, Institute for Animal Health, Pirbright, Surrey GU24 ONF, United Kingdom,2 Protein Science Group, Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom3

Received 6 July 2007/ Accepted 13 November 2007

The initial stage of foot-and-mouth disease virus (FMDV) infection is virus binding to cell surface integrins via the RGD motif in the GH loop of the VP1 capsid protein. As for all ligand/integrin interactions, the initial contact between FMDV and its integrin receptors is cation dependent and hence inhibited by EDTA. We have investigated this binding process with RGD-containing peptides derived from the VP1 capsid protein of FMDV and discovered that, upon binding, some of these peptides form highly stable, EDTA-resistant associations with integrin {alpha}vβ6. Peptides containing specific substitutions show that this stable binding is dependent on a helical structure immediately C terminal to the RGD and, specifically, two leucine residues at positions RGD +1 and RGD +4. These observations have a biological consequence, as we show further that stable, EDTA-resistant binding to {alpha}vβ6 is a property also exhibited by FMDV particles. Thus, the integrin-binding loop of FMDV appears to have evolved to form very stable complexes with the principal receptor of FMDV, integrin {alpha}vβ6. An ability to induce such stable complexes with its cellular receptor is likely to contribute significantly to the high infectiousness of FMDV.

* Corresponding author. Mailing address for John F. Marshall: Centre for Tumour Biology, Barts and the London Queen Mary's Medical and Dental School, Charterhouse Square, London EC1M 6BQ, United Kingdom. Phone: (44) 207 014 0407. Fax: (44) 207 014 0401. E-mail: John.Marshall{at}cancer.org.uk. Mailing address for Terry Jackson: Division of Microbiology, Institute for Animal Health, Pirbright, Surrey GU24 ONF, United Kingdom. Phone: (44) 1483 232441. Fax: (44) 1483 232448. E-mail: terry.jackson{at}bbsrc.ac.uk

{triangledown} Published ahead of print on 28 November 2007.

{ddagger} These authors contributed equally to this study.

{dagger} These authors jointly supervised this study.

Journal of Virology, February 2008, p. 1537-1546, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01480-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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