Within-Host Recombination in the Foot-and-Mouth Disease Virus Genome

Recombination is one of the determinants of genetic diversity in the foot-and-mouth disease virus (FMDV). FMDV sequences have a mosaic structure caused by extensive intra- and inter-serotype recombination, with the exception of the capsid-encoding region. While these genome-wide patterns of broad-scale recombination are well studied, not much is known about the patterns of recombination that may exist within infected hosts. In addition, detection of recombination among viruses evolving at the within-host level is challenging due to the similarity of the sequences and the limitations in differentiating recombination from point mutations. Here, we present the first analysis of recombination events between closely related FMDV sequences occurring within buffalo hosts. The detection of these events was made possible by the occurrence of co-infection of two viral swarms with about 1% nucleotide divergence. We found more than 15 recombination events, unequally distributed across eight samples from different animals. The distribution of these events along the FMDV genome was neither uniform nor related to the phylogenetic distribution of recombination breakpoints, suggesting a mismatch between within-host evolutionary pressures and long-term selection for infectivity and transmissibility.