Frontiers in Genetics ( IF 3.7 ) Pub Date : 2020-07-09 , DOI: 10.3389/fgene.2020.00828 Frances K Shepherd 1 , Cheryl M T Dvorak 1 , Michael P Murtaugh 1 , Douglas G Marthaler 2
Rotavirus A (RVA) remains one of the most widespread causes of diarrheal disease and mortality in piglets despite decades of research and efforts to boost lactogenic immunity for passive protection. Genetic changes at B cell epitopes (BCEs) may be driving failure of lactogenic immunity, which relies on production of IgA antibodies to passively neutralize RVA within the piglet gut, yet little research has mapped epitopes to swine-specific strains of RVA. Here we describe a bioinformatic approach to predict BCEs on the VP7 outer capsid protein using sequence data alone. We first validated the approach using a previously published dataset of VP7-specific cross-neutralization titers, and found that amino acid changes at predicted BCEs on the VP7 protein allowed for accurate recapitulation of antigenic relationships among the strains. Applying the approach to a dataset of swine RVA sequences identified 9 of the 11 known BCEs previously mapped to swine strains, indicating that epitope prediction can identify sites that are known to drive neutralization escape
中文翻译:
利用验证的计算机方法阐明基因型特异性VP7表位和猪轮状病毒A的抗原关系。
轮状病毒A(RVA)仍然是仔猪腹泻病和死亡率最广泛的原因之一,尽管数十年来进行了研究并努力提高用于被动保护的乳原性免疫力。B细胞表位(BCEs)的遗传变化可能是促乳汁免疫力失败的动力,这依赖于IgA抗体的产生来被动中和仔猪肠道内的RVA,但很少有研究将表位定位于猪特异性RVA株。在这里,我们描述了一种仅使用序列数据即可预测VP7外衣壳蛋白上BCE的生物信息学方法。我们首先使用以前发布的VP7特异性交叉中和效价数据集验证了该方法,并发现VP7蛋白上预测的BCE处的氨基酸变化允许准确重现菌株之间的抗原关系。