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Serotype-specific differences in antigenic regions of foot-and-mouth disease virus (FMDV): a comprehensive
Jessica N Cooke1, Kristi M Westover
1Department of Biology, Winthrop University, Rock Hill, SC 29733, USA.
Abstract:
Although vaccines are available for prophylaxis of foot-and-mouth disease virus (FMDV), few cases of escape mutants have been reported. To develop serotype-specific FMDV vaccination strategies it is imperative to understand how host selection has influenced evolution of FMDV. This study identified several possible targets for serotype-specific FMDV vaccines using a novel statistical approach. Pairs of closely related FMDV genomes identified in a phylogenetic analysis representing all seven serotypes were examined in order to understand the long term effects of host selection on well-characterized and predicted antigenic regions of importance (B, T(H), and T(C)). Estimates of synonymous and non-synonymous substitution rates for antigenic and non-antigenic regions were calculated for individual pairs of FMDV genomes. We found that on average, both antigenic and non-antigenic regions were subject to purifying selection acting at non-synonymous sites and that several antigenic sites showed a pattern of nucleotide substitution suggesting repeated positive selection across the population. In addition, we found that antigenic regions from the individual FMDV serotypes differed with respect to the extent of amino acid conservation. For a capsid T(H) epitope currently used in one synthetic vaccine, we found that serotypes SAT1-3 had significantly greater non-synonymous nucleotide substitutions than the other serotypes. In contrast, in a second well-studied B-cell epitope, there were no serotype-dependent differences in synonymous or non-synonymous nucleotide substitutions. These results support the hypothesis that host selection acting on individual serotypes has been an important factor in the long-term evolution FMDV and needs to be considered for vaccine design.
Insights
Understanding host selection is key for developing effective foot-and-mouth disease virus (FMDV) vaccines. This study reveals how FMDV evolves, identifying potential targets for serotype-specific vaccines to improve FMDV prophylaxis.
Area of Science:
- Virology
- Evolutionary Biology
- Immunology
Background:
- Foot-and-mouth disease virus (FMDV) poses a significant threat to livestock, necessitating effective vaccination strategies.
- Existing FMDV vaccines face challenges due to the emergence of escape mutants, highlighting the need for improved, serotype-specific approaches.
- Understanding the evolutionary pressures, particularly host selection, on FMDV is crucial for designing next-generation vaccines.
Purpose of the Study:
- To investigate the long-term effects of host selection on the evolution of antigenic regions within FMDV.
- To identify potential targets for serotype-specific FMDV vaccines by analyzing nucleotide substitution rates in key epitopes.
- To assess the role of host selection in driving FMDV diversity across its seven serotypes.
Main Methods:
- Phylogenetic analysis of FMDV genomes representing all seven serotypes.
- Calculation of synonymous and non-synonymous substitution rates for antigenic (B, T(H), T(C)) and non-antigenic regions.
- Comparative analysis of nucleotide substitution patterns across different FMDV serotypes and epitopes.
Main Results:
- Both antigenic and non-antigenic regions of FMDV are generally under purifying selection, but several antigenic sites show evidence of positive selection.
- Significant variation in amino acid conservation exists among antigenic regions across different FMDV serotypes.
- A T(H) epitope targeted by a synthetic vaccine exhibited higher non-synonymous substitutions in SAT1-3 serotypes, unlike a B-cell epitope.
Conclusions:
- Host selection is a significant driver of long-term FMDV evolution, influencing the diversity of its antigenic properties.
- The findings underscore the importance of considering serotype-specific evolutionary dynamics in the design of FMDV vaccines.
- Identifying and targeting rapidly evolving antigenic sites could lead to more robust and broadly protective FMDV vaccines.
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