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Integrin alphavbeta1 is a receptor for foot-and-mouth disease virus
Terry Jackson1, A Paul Mould, Dean Sheppard
1Department of Molecular Biology, Institute for Animal Health, Pirbright, Surrey GU24 ONF, UK. terry.jackson@bbsrc.ac.uk
Abstract:
Infection by field strains of Foot-and-mouth disease virus (FMDV) is initiated by binding to certain species of arginine-glycine-aspartic acid (RGD)-dependent integrin including alphavbeta3 and the epithelial integrin alphavbeta6. In this report we show that the integrin alphavbeta1, when expressed as a human/hamster heterodimer on transfected CHOB2 cells, is a receptor for FMDV. Virus binding and infection mediated by alphavbeta1 was inefficient in the presence of physiological concentrations of calcium and magnesium but were significantly enhanced by reagents that activate the integrin and promote ligand binding. The ability of chimeric alpha5/alphav integrin subunits, in association with the beta1 chain, to bind FMDV and mediate infection matched the ligand binding specificity of alphavbeta1, not alpha5beta1, thus providing further evidence for the receptor role of alphavbeta1. In addition, data are presented suggesting that amino acid residues near the RGD motif may be important for differentiating between the binding specificities of alphavbeta1 and alphavbeta6.
Insights
Foot-and-mouth disease virus (FMDV) uses integrin alphavbeta1 as a receptor for infection. This binding is enhanced by integrin activators, suggesting a new target for antiviral strategies.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Foot-and-mouth disease virus (FMDV) infects livestock, causing significant economic losses.
- FMDV infection initiates via binding to specific arginine-glycine-aspartic acid (RGD)-dependent integrins, such as alphavbeta3 and alphavbeta6.
- Understanding FMDV-integrin interactions is crucial for developing antiviral therapies.
Purpose of the Study:
- To investigate the role of integrin alphavbeta1 as a potential receptor for FMDV.
- To characterize the binding and infection mechanisms of FMDV mediated by alphavbeta1.
- To explore factors influencing FMDV binding to alphavbeta1.
Main Methods:
- Expression of human/hamster heterodimeric integrin alphavbeta1 on transfected CHOB2 cells.
- Assessing FMDV binding and infection mediated by alphavbeta1 under varying conditions (e.g., presence of divalent cations, activating reagents).
- Utilizing chimeric integrin subunits to confirm the specificity of alphavbeta1-mediated FMDV interaction.
Main Results:
- Integrin alphavbeta1 functions as a receptor for FMDV.
- FMDV binding and infection via alphavbeta1 were enhanced by integrin-activating reagents, particularly in the presence of physiological calcium and magnesium concentrations.
- Chimeric integrin studies confirmed the ligand-binding specificity of alphavbeta1 for FMDV.
Conclusions:
- Integrin alphavbeta1 is a functional receptor for FMDV.
- The efficiency of FMDV infection through alphavbeta1 is modulated by integrin activation status.
- Specific amino acid residues near the RGD motif may dictate the differential binding specificities of integrins like alphavbeta1 and alphavbeta6 for FMDV.