Evidence for positive selection in the capsid protein-coding region of thefoot-and-mouth disease virus (FMDV) subjected to experimental passage regimens

We present sequence data from two genomic regions of foot-and-mouth disease virus (FMDV) subjected to several experimental passage regimens. Maximum-l ikelihood estimates of the nonsynonymous-to-synonymous rate ratio parameter (d(N)/d(S)) suggested the action of positive selection on some antigenic s ites of the FMDV capsid during some experimental passages. These antigenic sites showed an accumulation of convergent amino acid replacements during m assive serial cytolytic passages and also in persistent infections of FMDV in cell culture. This accumulation was most significant at the antigenic si te A (the G-H loop of capsid VP1), which includes an Arg-Gly-Asp (RGD) cell ular recognition motif. Our analyses also identified a subregion of VP3, pa rt of the fivefold axis of FMDV particles, that also appeared to be subject ed to positive selection of amino acid replacements. From these results, we can conclude that under the restrictive conditions imposed either by the p resence of the monoclonal antibodies, by the persistent infections, or by t he competition processes established between different variants of the vira l population, amino acid replacement in some capsid-coding regions can be p ositively selected toward an increase of those mutants with a higher capabi lity to infect the cell.