Document details for 'Pervasive within-host recombination and epistasis as major determinants of the molecular evolution of the foot-and-mouth disease virus capsid'

Authors Ferretti, L., Perez-Martin, E., Zhang, F., Maree, F., De Klerk-Lorist, L.-M., Van Schalkwykc, L., Juleff, N., Charleston, B. and Ribeca, P
Publication details PLoS Pathogens 16(1), e1008235. PLoS.
Publisher details PLoS
Keywords DNA recombination, foot-and-mouth disease virus, buffaloes, linkage disequilibrium, epistasis, recombinant proteins
Abstract 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.
Last updated 2020-01-30
Links
  1. Article on publisher's site
    https://journals.plos.org/plospathogens/article/authors?id=10.1371/journal.ppat.1008235

Unless explicitly stated otherwise, all material is copyright © Biomathematics and Statistics Scotland.

Biomathematics and Statistics Scotland (BioSS) is formally part of The James Hutton Institute (JHI), a registered Scottish charity No. SC041796 and a company limited by guarantee No. SC374831. Registered Office: JHI, Invergowrie, Dundee, DD2 5DA, Scotland