Foot-and-mouth disease virus forms a highly stable, EDTA-resistant complex with its principal receptor, integrin alphavbeta6: implications for infectiousness.
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 alphavbeta6. 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 alphavbeta6 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 alphavbeta6. An ability to induce such stable complexes with its cellular receptor is likely to contribute significantly to the high infectiousness of FMDV.
Centre for Tumour Biology, Barts and the London Queen Mary's Medical and Dental School, Charterhouse Square, London EC1M 6BQ, United Kingdom.
Danielle
D
Dicara
Alison
A
Burman
Stuart
S
Clark
Stephen
S
Berryman
Mark J
MJ
Howard
Ian R
IR
Hart
John F
JF
Marshall
Terry
T
Jackson
D000951:Antigens, Neoplasm / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism*; D029544:Foot-and-Mouth Disease Virus / Q000502:physiology*; D016023:Integrins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011991:Receptors, Virus / Q000378:metabolism*; D053585:Virus Attachment
D000951:Antigens, Neoplasm; D036022:Capsid Proteins; D016023:Integrins; D011991:Receptors, Virus; C442501:VP1 protein, Foot-and-mouth disease virus; C073878:integrin alphavbeta6