Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Infect Genet Evol. 2020 Jul;81:104210. doi: 10.1016/j.meegid.2020.104210. Epub 2020 Jan 28.
Enterovirus 71 (EV71) is one of the main pathogens causing hand-foot-and-mouth disease (HFMD). The nose and mouth are usually the main infection entries of EV71 virus. However, its dynamic transport pathway from mouth to the whole body remains unknown. The reveal of this physiological mechanism in vivo will help to understand its transport direction, find its key proliferation nodes, and develop new preventive strategies. We trained a new strain of GFP-EV71 virus to be susceptible to mice brain by intracranial injection of mice. The adapted virus was oral-administrated to suckling mice. Then, the dynamic distributions of the virus in vivo were detected by living image system and fluorescence quantitation polymerase chain reaction (qPCR). We figured out the dynamic pathway of EV71 transport in vivo from intestine to peripheral tissue, then to the other organs. Small intestine was identified as a gateway for EV71 infection in vivo. Ileum was proved to be the main part of proliferation and transport of EV71 in small intestine of mice. EV71 was verified to enter small intestinal villus of mice through the infection of small intestinal epithelial cell. Acarbose displayed a good preventive effect on EV71 infection both in vivo and in vitro. Acarbose possibly decreased the intestinal infection of EV71 by blocking the receptor-binding sites on the surface of EV71 virion or by inhibiting various glycolic receptors on the cell surface. Thus, acarbose and its analogue may be the potential medicines to prevent EV71 infection.
肠道病毒 71 型（EV71）是引起手足口病（HFMD）的主要病原体之一。口鼻通常是 EV71 病毒的主要感染入口。然而，其从口腔到全身的动态传输途径尚不清楚。体内生理机制的揭示将有助于了解其传输方向，找到其关键增殖节点，并开发新的预防策略。我们通过向小鼠脑内注射，将一种新的 GFP-EV71 病毒株培养成对小鼠易感。适应后的病毒通过口服给予乳鼠。然后，通过活体成像系统和荧光定量聚合酶链反应（qPCR）检测病毒在体内的动态分布。我们发现 EV71 在体内从肠道到外周组织，再到其他器官的动态传输途径。小肠被确定为 EV71 体内感染的门户。回肠被证明是 EV71 在小鼠小肠中增殖和传输的主要部位。EV71 通过感染小肠上皮细胞进入小鼠小肠绒毛。阿卡波糖在体内和体外对 EV71 感染均显示出良好的预防作用。阿卡波糖可能通过阻断 EV71 病毒粒子表面的受体结合位点或通过抑制细胞表面上的各种糖酵解受体，从而减少 EV71 的肠道感染。因此，阿卡波糖及其类似物可能是预防 EV71 感染的潜在药物。
