Establishment and characterization of an oral gerbil model for a non-mouse-adapted enterovirus 71 strain
Establishment and characterization of an oral gerbil model for a non-mouse-adapted enterovirus 71 strain
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DOI：
10.1016/j.virusres.2018.07.008
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发表时间：
2018-08-15
期刊：
影响因子：
5
通讯作者：
Lu, Yi-Yu
中科院分区：
文献类型：
--
作者：
Li, Ci-Xiu;Zhang, Bing;Lu, Yi-Yu
肠道病毒71型（Enterovirus 71，EV 71）是引起手足口病（Handy，Foot，and Mouth Disease，HFMD）的主要病原体之一。建立合适的EV 71感染动物模型对研究EV 71的分布和致病机制具有重要意义。在这项研究中，我们建立了一个成功的感染的非小鼠适应分离的EV 71通过口服途径在7日龄长爪沙鼠（长爪沙鼠），所有这些都瘫痪，并在感染后10天内死亡。对12种组织中病毒载量的分析表明，病毒首先在感染后第1天的肠道、血液、心脏、肺和肌肉中检出，随后在随后的几天内在其余组织/器官中检出，其中胸腺、脾脏、脊髓和肌肉在感染后第5天的病毒滴度最高。病理检查显示骨骼肌和脊髓严重坏死，心肺水肿。感染和未感染沙鼠的各种组织的宿主基因表达的比较揭示了与抗病毒反应和病毒受体基因（唾液酸连接的聚糖）相关的基因的普遍上调，以及与神经元通信相关的基因的组织（肠道）特异性上调。以上结果表明，肠道病毒71可引起严重的神经系统并发症和全身大面积的组织损伤，表明7日龄沙鼠经口感染可作为研究肠道病毒71感染人类的合适动物模型。
Enterovirus 71 (EV71) is one of the major pathogens causing hand, foot, and mouth disease (HFMD) with neurological and systemic complications worldwide, and it is mostly discovered in infants and young children. It is of great significance to establish suitable animal models of EV71 infection on research of distribution and pathogenesis of the virus. In this study, we established a successful infection of a non-mouse-adapted isolate of EV71 via oral route in 7-day-old Mongolian gerbil (Meriones unguiculatus), all of which were paralyzed and died within 10 days post infection. Analysis of virus loads in twelve tissues showed that virus was first detected in intestine, blood, heart, lung, and muscle one day post-infection, and then in the rest of the tissues/organs within the next few days, among which thymus, spleen, spinal cord and muscles had the highest virus titer at 5 days post infection. Pathological examination showed that severe necrosis was observed in skeletal muscle and spinal cord, and edema was observed in both heart and lung. Comparisons of host gene expression of various tissues from infected and non-infected gerbils revealed a general up-regulation of genes related to anti-viral response and a viral receptor gene (sialic acid-linked glycans), as well as a tissue(gut)-specific up-regulation of genes related to neuronal communication. Collectively, our results showed that EV71 could induce severe neurological complications as well as massive tissue damage all over the body, which indicates that oral infection of 7-day gerbils can be a suitable animal model to study the infection of EV71 in human.