Enterovirus 71 (EV71) has become an important public health problem in the Asia-Pacific region in the past decades. EV71 infection might cause neurological and psychiatric complications and even death. Although an EV71 vaccine has been currently approved, there is no effective therapy for treating EV71-infected patients. Virus infections have been reported to shape host T cell receptor (TCR) repertoire. Therefore, understanding of host TCR repertoire in EV71 infection could better the knowledge in viral pathogenesis and further benefit the anti-viral therapy development. In this study, we used a mouse-adapted EV71 (mEV71) model to observe changes of host TCR repertoire in an EV71-infected central nervous system. Neonate mice were infected with mEV71 and mouse brainstem TCRβ repertoires were explored. Here, we reported that mEV71 infection impacted host brainstem TCRβ repertoire, where mEV71 infection skewed TCRβ diversity, changed VJ combination usages, and further expanded specific TCRβ CDR3 clones. Using bioinformatics analysis and ligand-binding prediction, we speculated the expanded TCRβ CDR3 clone harboring CASSLGANSDYTF sequence was capable of binding cleaved EV71 VP1 peptides in concert with major histocompatibility complex (MHC) molecules. We observed that mEV71 infection shaped host TCRβ repertoire and presumably expanded VP1-specific TCRβ CDR3 in mEV71-infected mouse brainstem that integrated EV71 pathogenesis in central nervous system.

中文翻译：

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肠病毒71感染影响宿主T细胞受体库，并可能扩展VP1特异性TCRβCDR3簇。

在过去的几十年中，肠道病毒71（EV71）已成为亚太地区重要的公共卫生问题。EV71感染可能会导致神经和精神并发症，甚至死亡。尽管目前已批准了EV71疫苗，但尚无有效的疗法可治疗EV71感染的患者。据报道，病毒感染会影响宿主T细胞受体（TCR）库。因此，了解宿主TCR库在EV71感染中可以更好地了解病毒的发病机理，并进一步有利于抗病毒治疗的发展。在这项研究中，我们使用了适应小鼠的EV71（mEV71）模型来观察感染EV71的中枢神经系统中宿主TCR组成的变化。用mEV71感染新生小鼠，并研究了小鼠脑干TCRβ的组成部分。这里，我们报道了mEV71感染影响了宿主脑干TCRβ库，其中mEV71感染歪曲了TCRβ多样性，改变了VJ组合用法，并进一步扩展了特定的TCRβCDR3克隆。使用生物信息学分析和配体结合预测，我们推测带有CASSLGANSDYTF序列的扩展TCRβCDR3克隆能够与主要的组织相容性复合体（MHC）分子结合，结合裂解的EV71 VP1肽。我们观察到，mEV71感染塑造了宿主TCRβ的库，并可能在受mEV71感染的小鼠脑干中扩展了VP1特异性TCRβCDR3，该小鼠脑干整合了EV71在中枢神经系统中的发病机制。使用生物信息学分析和配体结合预测，我们推测带有CASSLGANSDYTF序列的扩展TCRβCDR3克隆能够与主要的组织相容性复合体（MHC）分子结合，结合裂解的EV71 VP1肽。我们观察到，mEV71感染塑造了宿主TCRβ的库，并可能在受mEV71感染的小鼠脑干中扩展了VP1特异性TCRβCDR3，该小鼠脑干整合了EV71在中枢神经系统的发病机制。使用生物信息学分析和配体结合预测，我们推测了带有CASSLGANSDYTF序列的扩展TCRβCDR3克隆能够与主要的组织相容性复合物（MHC）分子结合，结合裂解的EV71 VP1肽。我们观察到，mEV71感染塑造了宿主TCRβ的库，并可能在受mEV71感染的小鼠脑干中扩展了VP1特异性TCRβCDR3，该小鼠脑干整合了EV71在中枢神经系统中的发病机制。