Specificity of the VP1 GH loop of Foot-and-Mouth Disease virus for alphav integrins.

Burman, A; Clark, S; Abrescia, N; Fry, E; Stuart, D; Jackson, T

Journal article

Specificity of the VP1 GH loop of Foot-and-Mouth Disease virus for alphav integrins.

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 alphavbeta6 or alphavbeta8 but not for inhibition of virus binding to alphavbeta3. 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 alphavbeta6. In contrast, although RGDM-containing peptides were effective for alphavbeta8, RGDR-containing peptides were not. These observations were confirmed by showing that a virus containing an RGDR motif uses alphavbeta8 less efficiently than alphavbeta6 as a receptor for infection. Finally, evidence is presented that shows alphavbeta3 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 alphavbeta6 with a higher affinity than to alphavbeta3 and alphavbeta8.

Publication status:: Published

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APA Style

Burman, A., Clark, S., Abrescia, N., Fry, E., Stuart, D., & Jackson, T. (2006). Specificity of the VP1 GH loop of Foot-and-Mouth Disease virus for alphav integrins. Journal of Virology, 80(19), 9798–9810.

MLA Style

Burman, A, et al. “Specificity of the VP1 GH Loop of Foot-and-Mouth Disease Virus for Alphav Integrins.” Journal of Virology, vol. 80, no. 19, 2006, pp. 9798–810.

Chicago Style

Burman, A, S Clark, N Abrescia, E Fry, D Stuart, and T Jackson. 2006. “Specificity of the VP1 GH Loop of Foot-and-Mouth Disease Virus for Alphav Integrins.” Journal of Virology 80 (19): 9798–9810.
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