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Journal of Virology, May 2001, p. 4158-4164, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4158-4164.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Role of the Cytoplasmic Domain of the beta -Subunit of Integrin alpha vbeta 6 in Infection by Foot-and-Mouth Disease Virus

Laura C. Miller,1 Wendy Blakemore,1 Dean Sheppard,2 Amha Atakilit,2 Andrew M. Q. King,1 and Terry Jackson1,*

Pirbright Laboratory, Institute for Animal Health, Pirbright, Surrey GU24 ONF, United Kingdom,1 and Lung Biology Center, Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco, California 94143-08542

Received 17 November 2000/Accepted 9 February 2001

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, alpha vbeta 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 alpha vbeta 6 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 beta 6 cytoplasmic domain on infection. Our results show that although loss of the beta 6 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 alpha vbeta 6-mediated infection was confirmed by experiments showing that infection could be blocked by concanamycin A, a specific inhibitor of the vacuolar ATPase.

* Corresponding author. Mailing address: Pirbright Laboratory, Institute for Animal Health, Ash Rd., Pirbright, Surrey GU24 ONF, United Kingdom. Phone: 44-1483-232441. Fax: 44-1483-237161. E-mail: terry.jackson{at}bbsrc.ac.uk.

Journal of Virology, May 2001, p. 4158-4164, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4158-4164.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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