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Journal of Virology, May 2004, p. 4533-4540, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4533-4540.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Integrin {alpha}vß8 Functions as a Receptor for Foot-and-Mouth Disease Virus: Role of the ß-Chain Cytodomain in Integrin-Mediated Infection

Terry Jackson,1* Stuart Clark,1 Stephen Berryman,1 Alison Burman,1 Stephanie Cambier,2 Dezhi Mu,2 Stephen Nishimura,2 and Andrew M. Q. King1

Department of Molecular Biology, Institute for Animal Health, Pirbright, Surrey GU24 ONF, United Kingdom,1 Department of Pathology, University of California at San Francisco, San Francisco, California 941432

Received 22 September 2003/ Accepted 5 January 2004

Field isolates of foot-and-mouth disease virus (FMDV) have been shown to use three {alpha}v integrins, {alpha}vß1, {alpha}vß3, and {alpha}vß6, as cellular receptors. Binding to the integrin is mediated by a highly conserved RGD motif located on a surface-exposed loop of VP1. The RGD tripeptide is recognized by several other members of the integrin family, which therefore have the potential to act as receptors for FMDV. Here we show that SW480 cells are made susceptible to FMDV following transfection with human ß8 cDNA and expression of {alpha}vß8 at the cell surface. The involvement of {alpha}vß8 in infection was confirmed by showing that virus binding and infection of the transfected cells are inhibited by RGD-containing peptides and by function-blocking monoclonal antibodies specific for either the {alpha}vß8 heterodimer or the {alpha}v chain. Similar results were obtained with a chimeric {alpha}vß8 including the ß6 cytodomain ({alpha}vß8/6), showing that the ß6 cytodomain can substitute efficiently for the corresponding region of ß8. In contrast, virus binding to {alpha}vß6 including the ß8 cytodomain ({alpha}vß6/8) was lower than that of the wild-type integrin, and this binding did not lead to infection. Further, the {alpha}vß6 chimera was recognized poorly by antibodies specific for the ectodomain of {alpha}vß6 and displayed a relaxed sequence-binding specificity relative to that of wild-type integrin. These data suggest that the ß6 cytodomain is important for maintaining {alpha}vß6 in a conformation required for productive infection by FMDV.

* Corresponding author. Mailing address: Pirbright Laboratory, Institute for Animal Health, Ash Rd., Pirbright, Surrey GU24 0NF, United Kingdom. Phone: 44 1483-232441. Fax: 44 1483-237161. E-mail: terry.jackson{at}bbsrc.ac.uk.

Journal of Virology, May 2004, p. 4533-4540, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4533-4540.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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