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Journal of Virology, November 2006, p. 11274-11282, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01236-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Molecular Epidemiology of the Foot-and-Mouth Disease Virus Outbreak in the United Kingdom in 2001{triangledown}

Eleanor M. Cottam,1,2* Daniel T. Haydon,2 David J. Paton,1 John Gloster,4,{dagger} John W. Wilesmith,3 Nigel P. Ferris,1 Geoff H. Hutchings,1 and Donald P. King1

Institute for Animal Health, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom,1 Division of Environmental and Evolutionary Biology, University of Glasgow, Glasgow G12 8QQ, United Kingdom,2 Animal Health and Welfare, Defra, 1a Page Street, London SW1P 4PQ, United Kingdom,3 Met Office, FitzRoy Road, Exeter, Devon EX1 3PB, United Kingdom4

Received 13 June 2006/ Accepted 30 August 2006

The objective of this study was to quantify the extent to which the genetic diversity of foot-and-mouth disease virus (FMDV) arising over the course of infection of an individual animal becomes fixed, is transmitted to other animals, and thereby accumulates over the course of an outbreak. Complete consensus sequences of 23 genomes (each of 8,200 nucleotides) of FMDV were recovered directly from epithelium tissue acquired from 21 farms infected over a nearly 7-month period during the 2001 FMDV outbreak in the United Kingdom. An analysis of these consensus sequences revealed very few apparently ambiguous sites but clear evidence of 197 nucleotide substitutions at 191 different sites. We estimated the rate of nucleotide substitution to be 2.26 x 10–5 per site per day (95% confidence interval [CI], 1.75 x 10–5 to 2.80 x 10–5) and nucleotide substitutions to accrue in the consensus sequence at an average rate of 1.5 substitutions per farm infection. This is a sufficiently high rate showing that detailed histories of the transmission pathways can be reliably reconstructed. Coalescent methods indicated that the date at which FMDV first infected livestock in the United Kingdom was 7 February 2001 (95% CI, 20 January to 19 February 2001), which was identical to estimates obtained on the basis of purely clinical evidence. Nucleotide changes appeared to have occurred evenly across the genome, and within the open reading frame, the ratio of nonsynonymous-to-synonymous change was 0.09. The ability to recover particular transmission pathways of acutely acting RNA pathogens from genetic data will help resolve uncertainties about how virus is spread and could help in the control of future epidemics.

* Corresponding author. Mailing address: Institute for Animal Health, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom. Phone: 44 1483 23 1129. Fax: 44 1483 23 1142. E-mail: eleanor.cottam{at}bbsrc.ac.uk.

{triangledown} Published ahead of print on 13 September 2006.

{dagger} Present address: Institute for Animal Health, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom.

Journal of Virology, November 2006, p. 11274-11282, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01236-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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