Role of the cytoplasmic domain of the beta-subunit of integrin alpha nu beta 6 in infection by foot-and-mouth disease virus

Field isolates of foot-and-mouth disease virus (FMDV) are believed to use R GD-dependent integrins as cellular receptors in vivo. Using SW480 cell tran sfectants, we have recently established that one such integrin, alphav beta 6, 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 alphav b eta6 receptor itself participated in the events that follow virus binding t o the host cell. In the present study, we investigated the effects of vario us deletion mutations in the beta6 cytoplasmic domain on infection. Our res ults show that although loss of the beta6 cytoplasmic domain has little eff ect on virus binding, this domain is essential for infection, indicating a critical role in postattachment events. The importance of endosomal acidifi cation in alphav beta6-mediated infection was confirmed by experiments show ing that infection could be blocked by concanamycin A, a specific inhibitor of the vacuolar ATPase.