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.
Highlights
The poor fidelity and lack of proofreading activity of the polymerases of RNA viruses cause high rates of spontaneous mutation during virus replication
The practical use of these tools to confidently reconstruct transmission trees during FMD outbreaks is limited by our understanding of the genetic diversity of viruses that exist within different epidemiological units under field conditions (Orton et al, 2013)
This study has investigated the genetic variability of viruses from field samples collected from the Foot-and-mouth disease virus (FMDV) outbreaks that occurred in the Southeast of the United Kingdom (UK) between the 3rd of August and the 30th of September 2007 (Cottam et al, 2008b; Ryan et al, 2008)
Summary
The poor fidelity and lack of proofreading activity of the polymerases of RNA viruses cause high rates of spontaneous mutation during virus replication. These rates are estimated to range from 10À5 to 2 Â 10À3 mutations per nucleotide per replication event (Thebaud et al, 2010) As a consequence, these viruses evolve rapidly and have high degrees of genome variability, which is a constant challenge for molecular diagnosic tests, as well as for prophylaxis and control methods such as vaccines and antivirals. These viruses evolve rapidly and have high degrees of genome variability, which is a constant challenge for molecular diagnosic tests, as well as for prophylaxis and control methods such as vaccines and antivirals These high evolution rates have been exploited to understand the transmission of human and animal RNA virus infections across fine spatial and temporal scales These studies help to increase the knowledge on virus evolution and to identify and analyse the potential origins, patterns of transmission and spread and risks of virus infections to be ready for the prediction, early detection and/or control of the disease
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