Pulmonary edema following central nervous system lesions induced by a non- mouse-adapted EV71 strain in neonatal BALB/c mice
Authors: Guangcai Duan
Rongguang Zhang
Jiehui Zhu
Chao Zhang
Haiyan Yang
Dejian Dang
Huifen Feng
Guangyuan Zhou
Jingchao Ren
Yuanlin Xi
Shuaiyin Chen
Yuefei Jin
Meili Sui
Journal: Virology Journal (2017)
Discipline: MICROBIOLOGY
Keywords: Central nervous system; Enterovirus 71; Hand foot and mouth disease; Pulmonary edema.
Affiliations: 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., Department of Epidemiology, College of Public Health, Xinxiang Medical University, Xinxiang, People's Republic of China., Department of Infectious Diseases, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China., Department of Epidemiology, College of Public Health, Zhengzhou University, No.100 Kexue Avenue, Zhengzhou, Henan, 450001, China. .

Abstract:  Background: 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. Methods: 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. Results: 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 × 106 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 &lt; 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 &lt; 0.05). Conclusions: 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. 

Retracted: No

PubPeer comments:
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