Neurovirology Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, 156-8506, Tokyo, Japan.
Department of Pathology, University of Malaya, Lembah Pantai, 59100, Kuala Lumpur, Malaysia.
Biochem Biophys Res Commun. 2022 Oct 20;626:72-78. doi: 10.1016/j.bbrc.2022.08.015. Epub 2022 Aug 10.
Poliovirus (PV) can spread through neural pathway to the central nervous system and replicates in motor neurons, which leads to poliomyelitis. Enterovirus 71 (EV71), which is closely related to PV, is one of the causative agents of hand-foot-and-mouth disease and can cause severe neurological diseases similar to poliomyelitis. Since PV is similar to EV71 in its motor neurotoxicity, we tried to understand if the results obtained with PV are of general applicability to EV71 and other viruses with similar characteristics. Using microfluidic devices, we demonstrated that both PV capsid and the PV genome undergo axonal retrograde transport with human PV receptor (hPVR), and the transported virus replicated in the soma of hPVR-expressing motor neurons. Similar to PV in hPVR-transgenic (Tg) mice, neural pathway ensuring spreading of EV71 has been shown in adult human scavenger receptor class B, member 2 (hSCARB2)-Tg mice. We have validated this finding in microfluidic devices by showing that EV71 is retrogradely transported together with hSCARB2 to the cell body where it replicates in an hSCARB2-dependent manner.
脊髓灰质炎病毒（PV）可通过神经途径传播到中枢神经系统并在运动神经元中复制，导致脊髓灰质炎。与 PV 密切相关的肠道病毒 71（EV71）是手足口病的病原体之一，可引起类似脊髓灰质炎的严重神经系统疾病。由于 PV 在运动神经毒性方面与 EV71 相似，我们试图了解用 PV 获得的结果是否普遍适用于 EV71 和其他具有相似特征的病毒。我们使用微流控装置证明，PV 衣壳和 PV 基因组都与人 PV 受体（hPVR）一起沿轴突逆行转运，并且转运的病毒在表达 hPVR 的运动神经元的体部中复制。与 hPVR 转基因（Tg）小鼠中的 PV 相似，在成年人类清道夫受体 B 类成员 2（hSCARB2）-Tg 小鼠中已经显示出确保 EV71 传播的神经途径。我们通过显示 EV71 与 hSCARB2 一起沿轴突逆行转运到细胞体并以 hSCARB2 依赖的方式在其中复制，在微流控装置中验证了这一发现。
