The in silico prediction of foot-and-mouth disease virus (FMDV) epitopes on the South African territories (SAT)1, SAT2 and SAT3 serotypes

摘要

Foot-and-mouth disease (FMD) is a highly contagious and economicallyimportant disease that affects even-toed hoofed mammals. The FMD virus(FMDV) is the causative agent of FMD, of which there are seven clinicallyindistinguishable serotypes. Three serotypes, namely, South AfricanTerritories (SAT)1, SAT2 and SAT3 are endemic to southern Africa and arethe most antigenically diverse among the FMDV serotypes. A negativeconsequence of this antigenic variation is that infection or vaccination withone virus may not provide immune protection from other strains or it may onlyconfer partial protection. The identification of B-cell epitopes is therefore keyto rationally designing cross-reactive vaccines that recognize theimmunologically distinct serotypes present within the population.Computational epitope prediction methods that exploit the inherent physicochemical properties of epitopes in their algorithms have beenproposed as a cost and time-effective alternative to the classical experimentalmethods. The aim of this project is to employ in silico epitope predictionprogrammes to predict B-cell epitopes on the capsids of the SAT serotypes.Sequence data for 18 immunologically distinct SAT1, SAT2 and SAT3 strains from across southern Africa were collated. Since, only one SAT1 virus hashad its structure elucidated by X-ray crystallography (PDB ID: 2WZR),homology models of the 18 virus capsids were built computationally usingModeller v9.12. They were then subjected to energy minimizations using theAMBER force field. The quality of the models was evaluated and validatedstereochemically and energetically using the PROMOTIF and ANOLEAservers respectively. The homology models were subsequently used as inputto two different epitope prediction servers, namely Discotope1.0 and Ellipro.Only those epitopes predicted by both programmes were defined as epitopes.Both previously characterised and novel epitopes were predicted on the SATstrains. Some of the novel epitopes are located on the same loops asexperimentally derived epitopes, while others are located on a putative novel antigenic site, which is located close to the five-fold axis of symmetry. Aconsensus set of 11 epitopes that are common on at least 15 out of 18 SATstrains was collated. In future work, the epitopes predicted in this study will beexperimentally validated using mutagenesis studies. Those found to be trueepitopes may be used in the rational design of broadly reactive SAT vaccines