The evolution of within-host population structure of Foot-and-Mouth Disease Virus during serial transmission in bovine hosts

RNA virus populations within samples are highly heterogeneous, containing a large number of minority sequence variants which can potentially be transmitted to other susceptible hosts. Consequently, consensus genome sequences provide an incomplete picture of within- and between-host viral population genetics and in particular we know remarkably little of the micro-evolutionary dynamics of viral populations during transmission. Foot-and-Mouth Disease Virus (FMDV) is an RNA virus that can spread through the circulatory system of a host to create multiple lesions in distant epithelia, each of them potentially undergoing independent evolution and seeding subsequent transmission events. Using the Illumina Genome Analyzer platform, we sequenced 18 samples of FMDV collected from a chain of sequentially infected cattle to obtain snap-shots of the evolving population structures within these different hosts and understand how the population structures are influenced by transmission. Analyses of the mutation spectra of the samples reveal polymorphisms >0.5% at between 21 and 146 sites across the genome, while 13 sites acquire mutations in excess of consensus frequency (50%). The results highlight that a number of minority variants can be transmitted during host-to-host infection events, while the size of the bottlenecks appear to be smaller between samples from the same host. This suggests strong intra-host founding effects and a rich within-host viral diversity. The dynamics of minority variants are dominated by genetic drift rather than a strong selective pressure, with the consequence that populations collected in the same host can be more divergent than populations observed in different hosts.