Within-host recombination in structural proteins of the Foot-and-Mouth Disease Virus

It is well known that recombination between different serotypes generates a mosaic structure in the FMDV genome. Such mosaic structure is clearly visible in the sequence of non-structural proteins and at the genomic boundaries between structural and non-structural proteins. Recombination also occurs among structural proteins, but appears to be strongly suppressed at phylogenetic scales, and only a few events have been observed. Here we show that co-inoculation of closely related strains in buffalos results in extensive within-host recombination within structural proteins during the infection process. For the first time, we are able to build a high-resolution map of effective within-host recombination rates in capsid genes. The effective recombination rate in VP1 during the acute infection phase is about 0.1 per base per year, i.e. comparable to the mutation/substitution rate. We find that the linkage disequilibrium pattern inside VP1 points to a mosaic structure with two main genetic blocks. Epistatic interactions between mutations appear to be present both within and between blocks. Overall our findings show that within the host capsid genes recombine at a high rate during FMDV co-infections.