This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Berryman, S. Articles by Jackson, T. Search for Related Content PubMed PubMed Citation Articles by Berryman, S. Articles by Jackson, T.

 Previous Article  |  Next Article 

Journal of Virology, July 2005, p. 8519-8534, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.8519-8534.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Early Events in Integrin vß6-Mediated Cell Entry of Foot-and-Mouth Disease Virus

Mammalian Virology,¹ Bio-imaging, Institute for Animal Health, Pirbright, Surrey GU24 ONF, United Kingdom²

Received 15 November 2004/ Accepted 7 March 2005

We have shown that foot-and-mouth disease virus (FMDV) infection mediated by the integrin vß6 takes place through clathrin-dependent endocytosis but not caveolae or other endocytic pathways that depend on lipid rafts. Inhibition of clathrin-dependent endocytosis by sucrose treatment or expression of a dominant-negative version of AP180 inhibited virus entry and infection. Similarly, inhibition of endosomal acidification inhibited an early step in infection. Blocking endosomal acidification did not interfere with surface expression of vß6, virus binding to the cells, uptake of the virus into endosomes, or cytoplasmic virus replication, suggesting that the low pH within endosomes is a prerequisite for delivery of viral RNA into the cytosol. Using immunofluorescence confocal microscopy, FMDV colocalized with vß6 at the cell surface but not with the B subunit of cholera toxin, a marker for lipid rafts. At 37°C, virus was rapidly taken up into the cells and colocalized with markers for early and recycling endosomes but not with a marker for lysosomes, suggesting that infection occurs from within the early or recycling endosomal compartments. This conclusion was supported by the observation that FMDV infection is not inhibited by nocodazole, a reagent that inhibits vesicular trafficking between early and late endosomes (and hence trafficking to lysosomes). The integrin vß6 was also seen to accumulate in early and recycling endosomes on virus entry, suggesting that the integrin serves not only as an attachment receptor but also to deliver the virus to the acidic endosomes. These findings are all consistent with FMDV infection proceeding via clathrin-dependent endocytosis.

This article has been cited by other articles:

• Martin, V., Domingo, E. (2008). Influence of the Mutant Spectrum in Viral Evolution: Focused Selection of Antigenic Variants in a Reconstructed Viral Quasispecies. Mol Biol Evol 25: 1544-1554 [Abstract] [Full Text]  
• DiCara, D., Burman, A., Clark, S., Berryman, S., Howard, M. J., Hart, I. R., Marshall, J. F., Jackson, T. (2008). Foot-and-Mouth Disease Virus Forms a Highly Stable, EDTA-Resistant Complex with Its Principal Receptor, Integrin {alpha}v 6: Implications for Infectiousness. J. Virol. 82: 1537-1546 [Abstract] [Full Text]  
• Nunez, J. I., Molina, N., Baranowski, E., Domingo, E., Clark, S., Burman, A., Berryman, S., Jackson, T., Sobrino, F. (2007). Guinea Pig-Adapted Foot-and-Mouth Disease Virus with Altered Receptor Recognition Can Productively Infect a Natural Host. J. Virol. 81: 8497-8506 [Abstract] [Full Text]  
• Ramsay, A. G., Keppler, M. D., Jazayeri, M., Thomas, G. J., Parsons, M., Violette, S., Weinreb, P., Hart, I. R., Marshall, J. F. (2007). HS1-Associated Protein X-1 Regulates Carcinoma Cell Migration and Invasion via Clathrin-Mediated Endocytosis of Integrin {alpha}v{beta}6. Cancer Res. 67: 5275-5284 [Abstract] [Full Text]  
• Ning, Y., Buranda, T., Hudson, L. G. (2007). Activated Epidermal Growth Factor Receptor Induces Integrin {alpha}2 Internalization via Caveolae/Raft-dependent Endocytic Pathway. J. Biol. Chem. 282: 6380-6387 [Abstract] [Full Text]  
• Burman, A., Clark, S., Abrescia, N. G. A., Fry, E. E., Stuart, D. I., Jackson, T. (2006). Specificity of the VP1 GH Loop of Foot-and-Mouth Disease Virus for {alpha}v Integrins. J. Virol. 80: 9798-9810 [Abstract] [Full Text]  
• Pellinen, T., Ivaska, J. (2006). Integrin traffic.. J. Cell Sci. 119: 3723-3731 [Abstract] [Full Text]  
• Stuart, A. D., Brown, T. D. K. (2006). Entry of feline calicivirus is dependent on clathrin-mediated endocytosis and acidification in endosomes.. J. Virol. 80: 7500-7509 [Abstract] [Full Text]