title: The impact of within-herd genetic variation upon inferred transmission trees for foot-and-mouth disease virus.
abstract: Full-genome sequences have been used to monitor the fine-scale dynamics of epidemics caused by RNA viruses. However, the ability of this approach to confidently reconstruct transmission trees is limited by the knowledge of the genetic diversity of viruses that exist within different epidemiological units. In order to address this question, this study investigated the variability of 45 foot-and-mouth disease virus (FMDV) genome sequences (from 33 animals) that were collected during 2007 from eight premises (10 different herds) in the United Kingdom. Bayesian and statistical parsimony analysis demonstrated that these sequences exhibited clustering which was consistent with a transmission scenario describing herd-to-herd spread of the virus. As an alternative to analysing all of the available samples in future epidemics, the impact of randomly selecting one sequence from each of these herds was used to assess cost-effective methods that might be used to infer transmission trees during FMD outbreaks. Using these approaches, 85% and 91% of the resulting topologies were either identical or differed by only one edge from a reference tree comprising all of the sequences generated within the outbreak. The sequence distances that accrued during sequential transmission events between epidemiological units was estimated to be 4.6 nucleotides, although the genetic variability between viruses recovered from chronic carrier animals was higher than between viruses from animals with acute-stage infection: an observation which poses challenges for the use of simple approaches to infer transmission trees. This study helps to develop strategies for sampling during FMD outbreaks, and provides data that will guide the development of further models to support control policies in the event of virus incursions into FMD free countries.
authors: The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom.
authors: Begoña
authors: B
authors: Valdazo-González
authors: The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom.
authors: Jan T
authors: JT
authors: Kim
authors: INRA, UR546 Biostatistics and Spatial Processes, F-84914 Avignon, France.
authors: Samuel
authors: S
authors: Soubeyrand
authors: The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom.
authors: Jemma
authors: J
authors: Wadsworth
authors: The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom.
authors: Nick J
authors: NJ
authors: Knowles
authors: Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: Daniel T
authors: DT
authors: Haydon
authors: The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom. Electronic address: donald.king@pirbright.ac.uk.
authors: Donald P
authors: DP
authors: King
mesh_terms: D000818:Animals; D001483:Base Sequence; D001499:Bayes Theorem; D002417:Cattle; D002418:Cattle Diseases / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D016000:Cluster Analysis; D004196:Disease Outbreaks / Q000662:veterinary; D005536:Foot-and-Mouth Disease / Q000635:transmission / Q000821:virology*; D029544:Foot-and-Mouth Disease Virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D014644:Genetic Variation; D016679:Genome, Viral; D008969:Molecular Sequence Data; D006113:United Kingdom / Q000453:epidemiology
keywords: Foot-and-mouth disease virus; Full genome; Transmission trees; Within-herd genetic variation