Beyond the consensus: dissecting within-host viral population diversity of foot-and-mouth disease virus using next-generation genome sequencing

Wright, C.F., Morelli, M.J., Thebaud, G., Knowles, N.J., Herzyk, P. , Paton, D.J., Haydon, D.T. and King, D.P. (2011) Beyond the consensus: dissecting within-host viral population diversity of foot-and-mouth disease virus using next-generation genome sequencing. Journal of Virology, 85(5), pp. 2266-2275. (doi: 10.1128/JVI.01396-10) (PMID:21159860) (PMCID:PMC3067773)

Full text not currently available from Enlighten.

Publisher's URL: http://dx.doi.org/10.1128/JVI.01396-10

Abstract

The sequence diversity of viral populations within individual hosts is the starting material for selection and subsequent evolution of RNA viruses such as foot-and-mouth disease virus (FMDV). Using next-generation sequencing (NGS) performed on a Genome Analyzer platform (Illumina), this study compared the viral populations within two bovine epithelial samples (foot lesions) from a single animal with the Inoculum used to initiate experimental infection. Genomic sequences were determined in duplicate sequencing runs, and the consensus sequence determined by NGS, for the Inoculum, was identical to that previously determined using the Sanger method. However, NGS reveals the fine polymorphic sub-structure of the viral population, from nucleotide variants present at just below 50% frequency to those present at fractions of 1%. Some of the higher frequency polymorphisms identified encoded changes within codons associated with heparan sulphate binding and were present in both feet lesions revealing intermediate stages in the evolution of a tissue-culture adapted virus replicating within a mammalian host. We identified 2,622, 1,434 and 1,703 polymorphisms in the Inoculum, and in the two foot lesions respectively: most of the substitutions occurred only in a small fraction of the population and represent the progeny from recent cellular replication prior to onset of any selective pressures. We estimated an upper limit for the genome-wide mutation rate of the virus within a cell to be 7.8 x 10-4 per nt. The greater depth of detection, achieved by NGS, demonstrates that this method is a powerful and valuable tool for the dissection of FMDV populations within-hosts

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Haydon, Professor Daniel and Morelli, Dr Marco and Herzyk, Dr Pawel and Thebaud, Dr Gael
Authors: Wright, C.F., Morelli, M.J., Thebaud, G., Knowles, N.J., Herzyk, P., Paton, D.J., Haydon, D.T., and King, D.P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Journal of Virology
ISSN:0022-538X

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
443881Population genetics and genomics of ovine parasitic nematodes and their application to the study of anthelmintic resistanceAndrew TaitBiotechnology and Biological Sciences Research Council (BBSRC)BB/E018505/1School of Veterinary Medicine
461341A systems biology approach to integrating pathogen evolution and epidemiologyDaniel HaydonBiotechnology and Biological Sciences Research Council (BBSRC)BB/F005733/1Institute of Biodiversity Animal Health and Comparative Medicine