1 research outputs found
Pervasive within-host recombination and epistasis as major determinants of the molecular evolution of the foot-and-mouth disease virus capsid
Although recombination is known to occur in foot-and-mouth disease virus (FMDV), it is
considered only a minor determinant of virus sequence diversity. Analysis at phylogenetic
scales shows inter-serotypic recombination events are rare, whereby recombination occurs
almost exclusively in non-structural proteins. In this study we have estimated recombination
rates within a natural host in an experimental setting. African buffaloes were inoculated with
a SAT-1 FMDV strain containing two major viral sub-populations differing in their capsid
sequence. This population structure enabled the detection of extensive within-host recombination
in the genomic region coding for structural proteins and allowed recombination rates
between the two sub-populations to be estimated. Quite surprisingly, the effective recombination
rate in VP1 during the acute infection phase turns out to be about 0.1 per base per
year, i.e. comparable to the mutation/substitution rate. Using a high-resolution map of effective
within-host recombination in the capsid-coding region, we identified a linkage disequilibrium
pattern in VP1 that is consistent with a mosaic structure with two main genetic blocks.
Positive epistatic interactions between co-evolved variants appear to be present both within
and between blocks. These interactions are due to intra-host selection both at the RNA and
protein level. Overall our findings show that during FMDV co-infections by closely related
strains, capsid-coding genes recombine within the host at a much higher rate than expected,
despite the presence of strong constraints dictated by the capsid structure. Although these
intra-host results are not immediately translatable to a phylogenetic setting, recombination and epistasis must play a major and so far underappreciated role in the molecular evolution
of the virus at all scales.File. Supplementary methods and figures. Supplementary Information containing further
details on statistical methods, data analysis and evolutionary consequences.Writing – review & editing: Luca Ferretti, Eva Pe´rez-Martı´n, Franc¸ois Maree, Bryan Charleston,
Paolo Ribeca.The Pirbright Institute receives grant aided
support from the Biotechnology and
Biological Sciences Research Council of the United Kingdom (projects BB/E/I/00007035, BB/E/I/
00007036, BB/E/I/00007032, BBS/E/I/00007039
and grant BB/L011085/1 as part of the joint USDANSF-
NIH-BBSRC Ecology and Evolution of
Infectious Diseases program).http://www.plospathogens.orgam2020Microbiology and Plant Patholog