The Epithelial Integrin αvβ6 Is a Receptor for Foot-and-Mouth Disease Virus

Field isolates of foot-and-mouth disease virus (FMDV) have been shown to use the RGD-dependent integrin αvβ3 as a cellular receptor on cultured cells. However, several other RGD-dependent integrins may have the potential to act as receptors for FMDV in vivo. Of these, αvβ6 is a likely candidate for use as a receptor by FMDV as it is expressed on epithelial cells, which correlates with the tissue tropism of the virus. In this report, we show that human colon carcinoma cells (SW480) that are normally nonpermissive for FMDV become susceptible to infection as a result of transfection with the integrin β6 subunit and expression of αvβ6 at the cell surface. Integrin αvβ6 is the major site for virus attachment on the β6-transfected cells, and binding to αvβ6 serves to increase the rate of virus entry into these cells. In addition, we show that virus binding and infection of the β6-transfected cells is mediated through an RGD-dependent interaction that is specifically inhibited by a monoclonal antibody (10D5) that recognizes αvβ6. These studies establish a role for αvβ6 as a cellular receptor for FMDV.