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 ROD-dependent integrin alpha v beta 3 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, alpha v beta 6 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 beta 6 subunit and expression of alpha v beta 6 at the cell surface. Integrin alpha v beta 6 is the major site for virus attachment on the beta 6-transfected cells, and binding to alpha v beta 6 serves to increase the rate of virus entry into these cells. In addition, we show that virus binding and infection of the beta 6-transfected cells is mediated through an RGD-dependent interaction that is specifically inhibited by a monoclonal antibody (10D5) that recognizes al beta 6. These studies establish a role for alpha v beta 6 as a cellular receptor for FM.