Cooke Jessica N, Westover Kristi M
Department of Biology, Winthrop University, Rock Hill, SC 29733, USA.
Infect Genet Evol. 2008 Dec;8(6):855-63. doi: 10.1016/j.meegid.2008.08.004. Epub 2008 Aug 23.
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.
尽管有疫苗可用于预防口蹄疫病毒（FMDV），但逃逸突变体的病例报道很少。为了制定血清型特异性FMDV疫苗接种策略，了解宿主选择如何影响FMDV的进化至关重要。本研究使用一种新的统计方法确定了几种血清型特异性FMDV疫苗的可能靶点。对系统发育分析中确定的代表所有七种血清型的密切相关FMDV基因组对进行了检查，以了解宿主选择对特征明确且预测的重要抗原区域（B、T(H)和T(C)）的长期影响。计算了FMDV基因组对中抗原和非抗原区域的同义替换率和非同义替换率估计值。我们发现，平均而言，抗原和非抗原区域在非同义位点都受到纯化选择的作用，并且几个抗原位点显示出核苷酸替换模式，表明在群体中反复出现正选择。此外，我们发现单个FMDV血清型的抗原区域在氨基酸保守程度方面存在差异。对于目前一种合成疫苗中使用的衣壳T(H)表位，我们发现血清型SAT1 - 3的非同义核苷酸替换明显多于其他血清型。相比之下，在另一个经过充分研究的B细胞表位中，同义或非同义核苷酸替换没有血清型依赖性差异。这些结果支持了这样一种假设，即作用于单个血清型的宿主选择是FMDV长期进化中的一个重要因素，在疫苗设计中需要加以考虑。
