Role of the Cytoplasmic Domain of the β-Subunit of Integrin αvβ6 in Infection by Foot-and-Mouth Disease Virus

Abstract

Field isolates of foot-and-mouth disease virus (FMDV) are believed to use RGD-dependent integrins as cellular receptors in vivo. Using SW480 cell transfectants, we have recently established that one such integrin, αvβ6, functions as a receptor for FMDV. This integrin was shown to function as a receptor for virus attachment. However, it was not known if the αvβ6 receptor itself participated in the events that follow virus binding to the host cell. In the present study, we investigated the effects of various deletion mutations in the β6 cytoplasmic domain on infection. Our results show that although loss of the β6 cytoplasmic domain has little effect on virus binding, this domain is essential for infection, indicating a critical role in postattachment events. The importance of endosomal acidification in αvβ6-mediated infection was confirmed by experiments showing that infection could be blocked by concanamycin A, a specific inhibitor of the vacuolar ATPase.