Fig 1.
Subconsensus variants present above 2% frequency in inoculum ultra-deep sequencing.
Reference is the consensus sequence of the inoculum and minority represents the polymorphic base at each site. Nucleotide variation was not detected in inoculum 2A and 3B1-3 coding regions. Sample count indicates the number of sample consensus sequences (of 52 total) that encoded each nucleotide found at the minority (2–49%) level in the inoculum deep sequence. Animal count indicates the number of individual hosts that provided sequences with these variants of the 13 total. If no value is indicated (-), no sample sequence encoded the inoculum’s minority nucleotide at the consensus level. Roman numerals and colors indicate the presence of each specific site change in at least one clade member as described in Results: Phylogenetic Associations.
Table 1.
Distribution of consensus-level nucleotide substitutions in sample viruses across the FMDV coding region in 52 sampled viruses.
Fig 2.
FMD virus change over the course of infection.
a) The total number of nucleotide substitutions present at the consensus level at each sampled time point compared to inoculum consensus b) Step-wise changes per day. The number of substitutions (nucleotide differences between each sample consensus and the previous sample consensus) divided by the number of elapsed days between samples plotted against each sample time since initial infection. Values from concurrent samples from the same animal (different tissues) were averaged. Overlapping data points were slightly offset for clarity. Early, Transitional, and Persistent phases of infection are described in methods.
Table 2.
Nucleotide substitution rates averaged across non-vaccinated and vaccinated cattle.
Fig 3.
Phylogenetic relationships between sampled virus consensuses.
An inoculum-rooted maximum likelihood tree was created using PhyML. Branch lengths are proportional to nucleotide differences. Clades have been delineated based upon the clusters present here. Abbreviations: dpi–days post-infection, Na–nasal secretion, Np–nasopharyngeal tissue, OPF–oropharyngeal fluid, Sa–saliva, Se–serum, Ves–epithelial vesicle.
Fig 4.
Consensus virus identity across infection.
Boxes along each animal’s timeline indicates a virus sample. Colors and associated Roman numerals indicate clades based on inferred phylogenetic relationships (see Fig 4). Inoculum at left has been hypothesized as the source of the seven variant viruses detected. Abbreviations: DPI–days post-infection, Na–nasal secretion, Np–nasopharyngeal tissue (necropsy), OPF–oropharyngeal fluid (probang cup sample), Sa–saliva, Se–serum, Ves–epithelial vesicle. Three phases of FMDV infection were used to define progression of infection in individual animals: early, transitional, and persistent periods; temporal boundaries for the phases differ in vaccinated and non-vaccinated animals, as described in methods.
Fig 5.
Consensus virus identity across infection.
Boxes along each animal’s timeline indicates a virus sample. Colors and associated Roman numerals indicate clades based on inferred phylogenetic relationships (see Fig 4). Inoculum at left has been hypothesized as the source of the seven variant viruses detected. Abbreviations: DPI–days post-infection, Na–nasal secretion, Np–nasopharyngeal tissue (necropsy), OPF–oropharyngeal fluid (probang cup sample), Sa–saliva, Se–serum, Ves–epithelial vesicle. Three phases of FMDV infection were used to define progression of infection in individual animals: early, transitional, and persistent periods; temporal boundaries for the phases differ in vaccinated and non-vaccinated animals, as described in methods.
Table 3.
Amino acid substitutions in FMDV capsid surface proteins.