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Journal of Virology, November 2008, p. 10556-10566, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00907-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Foot-and-Mouth Disease Virus, but Not Bovine Enterovirus, Targets the Host Cell Cytoskeleton via the Nonstructural Protein 3Cpro{triangledown}

Hannah Armer ,1,{dagger},{ddagger} Katy Moffat,1,{dagger} Thomas Wileman,1,2 Graham J. Belsham,1,3 Terry Jackson,1 W. Paul Duprex,4 Martin Ryan,5 and Paul Monaghan1*

Institute for Animal Health, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom,1 School of Medicine, Institute of Health, University of East Anglia, Norwich, Norfolk NR4 TJU, United Kingdom,2 National Veterinary Institute, Technical University of Denmark, Lindholm, 4771 Kalvehave, Denmark,3 School of Biomedical Sciences, The Queen's University of Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, United Kingdom,4 Division of Cell and Molecular Biology, University of St. Andrews, Irvine Building, North Street, St. Andrews, Fife KY16 9AL, United Kingdom5

Received 1 May 2008/ Accepted 13 August 2008

Foot-and-mouth disease virus (FMDV), a member of the Picornaviridae, is a pathogen of cloven-hoofed animals and causes a disease of major economic importance. Picornavirus-infected cells show changes in cell morphology and rearrangement of cytoplasmic membranes, which are a consequence of virus replication. We show here, by confocal immunofluorescence and electron microscopy, that the changes in morphology of FMDV-infected cells involve changes in the distribution of microtubule and intermediate filament components during infection. Despite the continued presence of centrosomes in infected cells, there is a loss of tethering of microtubules to the microtubule organizing center (MTOC) region. Loss of labeling for {gamma}-tubulin, but not pericentrin, from the MTOC suggests a targeting of {gamma}-tubulin (or associated proteins) rather than a total breakdown in MTOC structure. The identity of the FMDV protein(s) responsible was determined by the expression of individual viral nonstructural proteins and their precursors in uninfected cells. We report that the only viral nonstructural protein able to reproduce the loss of {gamma}-tubulin from the MTOC and the loss of integrity of the microtubule system is FMDV 3Cpro. In contrast, infection of cells with another picornavirus, bovine enterovirus, did not affect {gamma}-tubulin distribution, and the microtubule network remained relatively unaffected.

* Corresponding author. Mailing address: Institute for Animal Health, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom. Phone: 44 (0)1483 232441. Fax: 44 (0)1483 232448. E-mail: paul.monaghan{at}bbsrc.ac.uk

{triangledown} Published ahead of print on 27 August 2008.

{dagger} H.A. and K.M. contributed equally to this study.

{ddagger} Present address: London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.

Journal of Virology, November 2008, p. 10556-10566, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00907-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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