ABSTRACT

In 2014, enterovirus D68 (EV-D68) emerged causing outbreaks of severe respiratory disease in children worldwide. In a subset of patients, EV-D68 infection was associated with the development of central nervous system (CNS) complications, including acute flaccid myelitis (AFM). Since then, the number of reported outbreaks has risen biennially, which emphasizes the need to unravel the systemic pathogenesis in humans. We present here a comprehensive review on the different stages of the pathogenesis of EV-D68 infection – infection in the respiratory tract, systemic dissemination and infection of the CNS – based on observations in humans as well as experimental in vitro and in vivo studies. This review highlights the knowledge gaps on the mechanisms of systemic dissemination, routes of entry into the CNS and mechanisms to induce AFM or other CNS complications, as well as the role of virus and host factors in the pathogenesis of EV-D68.

摘要

2014 年，肠道病毒 D68 (EV-D68) 出现，导致全球儿童爆发严重的呼吸道疾病。在一部分患者中，EV-D68 感染与中枢神经系统 (CNS) 并发症的发展有关，包括急性弛缓性脊髓炎 (AFM)。从那时起，报告的暴发数量每两年增加一次，这强调了解开人类全身发病机制的必要性。我们在此全面回顾了 EV-D68 感染发病机制的不同阶段——呼吸道感染、全身传播和中枢神经系统感染——基于对人类的观察以及体外和体内实验学习。本综述强调了系统性传播机制、进入中枢神经系统的途径和诱发 AFM 或其他中枢神经系统并发症的机制以及病毒和宿主因素在 EV-D68 发病机制中的作用的知识空白。