Arginine-glycine-aspartic acid-specific binding by foot-and-mouth disease viruses to the purified integrin alpha v beta 3 in vitro

• Published in: Journal of virology Vol. 71; no. 11; pp. 8357 - 8361
• Main Authors: Jackson, T, Sharma, A, Ghazaleh, R A, Blakemore, W E, Ellard, F M, Simmons, D L, Newman, JWI, Stuart, DI, King, AMQ
• Format: Journal Article
• Language: English
• Published: 01.11.1997
• ISSN: 0022-538X
• DOI: 10.1128/JVI.71.11.8357-8361.1997

The integrin alpha v beta 3 has been shown to act as the receptor for internalization of foot-and-mouth disease virus (FMDV) (A12), with attachment being through a highly conserved RGD motif located on the G-H loop of viral capsid protein VP1. In addition, however, we have recently shown that efficient infection of culture-grown cells by FMDV (O1BFS) requires binding to cell surface heparan sulfate. In this study, we have used a solid-phase receptor binding assay to characterize the binding by FMDV to purified alpha v beta 3 in the absence of heparan sulfate and other cell surface components. In this assay, FMDV (O1BFS) successfully replicated authentic ligand binding by cellular alpha v beta 3 in terms of its high affinity, dependence on divalent cations, and activation by manganese ions. Virus binding to this preparation of alpha v beta 3 was exquisitely sensitive to competition by short RGD-containing peptides (50% inhibition at < 10 super(-8) M peptide), and this inhibition was highly sequence specific, with the equivalent RGE peptide being at least 10 super(4) fold less effective as a competitor. Representative viruses of the other six serotypes of FMDV bound to alpha v beta 3 in a similar RGD-specific manner, although significant differences in sensitivity to RGD peptides suggest that the affinity of the different FMDV serotypes for alpha v beta 3 is influenced, in part, by the variable amino acid residues in the VP1 G-H loop on either side of the RGD.