目前尚不清楚特定组织内肠道病毒复制的机制。虽然肠道病毒A71（EV-A71）和柯萨奇病毒A16（CV-A16）都是引起手足口病的常见病原体，但它们具有不同的神经病毒学特性。本文通过口服接种模型研究了内质网核糖体进入位点（IRES）在神经病毒性决定中的作用。在接种小鼠透卵泡EV-A71毒株（MP4）时，受体表达小鼠（hSCARB2-Tg）通过不同的行政途径后出现神经症状。胃肠道接种的MP4毒株引起了神经元损失和神经原纤维空泡化等病理变化，而更换为CV-A16的EV-A71 IRES则消除了神经病理表型。即使在腹腔和颅内接种的小鼠中，交换IRES的EV-A71的神经病毒性也有所削弱。不管接种路径如何，小鼠组织中都检测到较少的嵌合MP4病毒RNA和蛋白质。组织特异性的复制可以通过细胞基础特征表征。尽管嵌合MP4病毒在人类肠道C2BBe1和神经母细胞瘤SH-SY5Y细胞中复制较差，但在易感的横纹肌肉瘤细胞中的复制并没有受到影响。总的来说，我们的结果展示了IRES对EV-A71和CV-A16神经病毒性的影响，并强调IRES在组织热带病中的重要性以及宿主受体的作用。版权所有 © 2023 Elsevier Masson SAS出版。

The mechanisms underlying tissue-specific replication of enteroviruses are currently unclear. Although enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are both common pathogens that cause hand-foot-mouth disease, they display quite different neurotropic properties. Herein, we characterized the role of the internal ribosomal entry site (IRES) in determining neurovirulence using an oral inoculation model of EV-A71. The receptor transgenic (hSCARB2-Tg) mice developed neurological symptoms after being infected with a mouse-adapted EV-A71 strain (MP4) via different administrative routes. Intragastric administration of the MP4 strain caused pathological changes such as neuronal loss and neuropil vacuolation, whereas replacing EV-A71 IRES with CV-A16 abolished the neuropathological phenotypes. The attenuated neurotropic potential of IRES-swapped EV-A71 was observed even in mice that received intraperitoneal and intracerebral inoculations. Fewer chimeric MP4 viral RNAs and proteins were detected in the mouse tissues, regardless of the inoculation route. Tissue-specific replication can be reflected in cell-based characterization. While chimeric MP4 virus replicated poorly in human intestinal C2BBe1 and neuroblastoma SH-SY5Y cells, its replication in susceptible rhabdomyosarcoma cells was not affected. Overall, our results demonstrated that the IRES determined the neurotropic potential of EV-A71 and CV-A16, emphasizing the importance of the IRES in tissue tropism, along with the host receptors.Copyright © 2023. Published by Elsevier Masson SAS.