Tracking the antigenic evolution of foot-and-mouth disease virus

Loading...
Thumbnail Image

Authors

Reeve, Richard
Borley, Daryl W.
Maree, Francois Frederick
Upadhyaya, Sasmita
Lukhwareni, Azwidowi
Esterhuysen, Jan J.
Harvey, William T.
Blignaut, Belinda
Fry, Elizabeth E.
Parida, Satya

Journal Title

Journal ISSN

Volume Title

Publisher

Public Library of Science

Abstract

Quantifying and predicting the antigenic characteristics of a virus is something of a holy grail for infectious disease research because of its central importance to the emergence of new strains, the severity of outbreaks, and vaccine selection. However, these characteristics are defined by a complex interplay of viral and host factors so that phylogenetic measures of viral similarity are often poorly correlated to antigenic relationships. Here, we generate antigenic phylogenies that track the phenotypic evolution of two serotypes of footand- mouth disease virus by combining host serology and viral sequence data to identify sites that are critical to their antigenic evolution. For serotype SAT1, we validate our antigenic phylogeny against monoclonal antibody escape mutants, which match all of the predicted antigenic sites. For serotype O, we validate it against known sites where available, and otherwise directly evaluate the impact on antigenic phenotype of substitutions in predicted sites using reverse genetics and serology. We also highlight a critical and poorly understood problem for vaccine selection by revealing qualitative differences between assays that are often used interchangeably to determine antigenic match between field viruses and vaccine strains. Our approach provides a tool to identify naturally occurring antigenic substitutions, allowing us to track the genetic diversification and associated antigenic evolution of the virus. Despite the hugely important role vaccines have played in enhancing human and animal health, vaccinology remains a conspicuously empirical science. This study advances the field by providing guidance for tuning vaccine strains via site-directed mutagenesis through this high-resolution tracking of antigenic evolution of the virus between rare major shifts in phenotype.

Description

S1 Data. VNT serological results for serotype O viruses and antisera.
S2 Data. LPBE serological results for serotype O viruses and antisera.
S3 Data. VNT serological results for serotype SAT1 viruses and antisera.
S1 Table. Foot-and-mouth disease virus details with accession numbers.
S2 Table. Pan-serotypic reference alignment of FMDV. The dataset shows the aligned VP2, VP3 and VP1 proteins of example SAT1 and O isolates used in the study alongside representative isolates from the other five serotypes. The four contiguous surface-exposed structural motifs confirmed as containing antigenic sites on at least four serotypes are highlighted in red–locations are approximate due to structural differences between the serotypes. The RGD cell surface receptor-binding motif, in the centre of the third site, is highlighted in blue.
S3 Table. Residues identified as part of epitopes on structural proteins across the six tested serotypes of FMDV, along with corresponding positions on all serotypes.
S4 Table. SAT1 mar-mutants.

Keywords

Serotype SAT1, Serotype O, Infectious disease, Virus

Sustainable Development Goals

Citation

Reeve R, Borley DW, Maree FF, Upadhyaya S, Lukhwareni A, Esterhuysen JJ, et al. (2016) Tracking the Antigenic Evolution of Foot-and- Mouth Disease Virus. PLoS ONE 11(7): e0159360. DOI: 10.1371/journal.pone.0159360.