Department of Epidemiology, College of Public Health, Zhengzhou University, No.100 Kexue Avenue, Zhengzhou, Henan, 450001, China.
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang, People's Republic of China.
Virol J. 2017 Dec 28;14(1):243. doi: 10.1186/s12985-017-0911-5.
Enterovirus (EV) infection has been a serious health issue in Asia-Pacific region. It has been indicated that the occurrence of fatal hand foot and mouth disease (HFMD) cases following EV71 infection is mainly attributed to pulmonary edema. However, the development of pulmonary disorders after EV71 infection remains largely unknown. To establish an EV71-infected animal model and further explore the underlying association of central nervous system (CNS) invasion with pulmonary edema, we isolated a clinical source EV71 strain (ZZ1350) from a severe case in Henan Province.
We evaluated the cytotoxicity of ZZ1350 strain and the susceptibility in 3-day-old BALB/c mice with intraperitoneal, intracerebral and intramuscular inoculation. Various histopathological and immunohistochemical techniques were applied to determine the target organs or tissue damage after infection. Correlation analysis was used to identify the relationship between CNS injury and pulmonary disorders.
Our experimental results suggested that ZZ1350 (C4 subtype) had high cytotoxicity against African green monkey kidney (Vero) cells and human rhabdomyosarcoma (RD) cells and neonatal BALB/c mice were highly susceptible to the infection with ZZ1350 through three different inoculation routes (2 × 10 pfu/mouse) exhibiting severe neurological and respiratory symptoms that were similar to clinical observation. Viral replication was found in brain, spinal cord, skeletal muscle, lung, spleen, liver, heart of infected mice and these sections also showed histopathological changes. We found that brain histology score was positive correlated with lung histology score in total experimental mice and mice under the three inoculation routes (P < 0.05). At the same time, there were positive correlations between spinal cord score and lung score in total experimental mice and mice with intracerebral inoculation (P < 0.05).
ZZ1350 strain is effective to establish animal model of EV71 infection with severe neurological and respiratory symptoms. The development of pulmonary disorders after EV71 infection is associated with severity of CNS damage.
肠道病毒（EV）感染一直是亚太地区的一个严重健康问题。有研究表明，肠道病毒 71 型（EV71）感染后导致致命手足口病（HFMD）病例的发生主要归因于肺水肿。然而，EV71 感染后肺部疾病的发展仍知之甚少。为了建立 EV71 感染的动物模型，并进一步探讨中枢神经系统（CNS）入侵与肺水肿之间的潜在关联，我们从河南省的一例重症病例中分离出一株临床来源的 EV71 株（ZZ1350）。
我们评估了 ZZ1350 株的细胞毒性，并通过腹腔内、脑内和肌肉内接种，在 3 日龄 BALB/c 小鼠中评估其易感性。应用各种组织病理学和免疫组织化学技术来确定感染后的靶器官或组织损伤。采用相关分析来确定 CNS 损伤与肺部疾病之间的关系。
我们的实验结果表明，ZZ1350（C4 亚型）对非洲绿猴肾（Vero）细胞和人横纹肌肉瘤（RD）细胞具有高细胞毒性，新生 BALB/c 小鼠通过三种不同的接种途径（2×10 pfu/只）对 ZZ1350 感染高度敏感，表现出类似临床观察的严重神经和呼吸症状。病毒在感染小鼠的脑、脊髓、骨骼肌、肺、脾、肝、心等部位复制，并在这些部位出现组织病理学改变。我们发现，在总实验小鼠和三种接种途径的小鼠中，脑组织学评分与肺组织学评分呈正相关（P<0.05）。同时，在总实验小鼠和脑内接种的小鼠中，脊髓评分与肺评分之间存在正相关（P<0.05）。
ZZ1350 株可有效建立具有严重神经和呼吸症状的 EV71 感染动物模型。EV71 感染后肺部疾病的发生与 CNS 损伤的严重程度有关。
