The cross-reactivity of the enterovirus 71 to human brain tissue and identification of the cross-reactivity related fragments

Chun Shi Jia,Yan Feng Xu,Wan Bo Li,Shu Zhu Lin,Chun Mei Ma,Xiao Lin Liu,Lian Feng Zhang,Yi Hao,Chuan Qin,Xue Zhong Gao,Jiang Ning Liu

doi:10.1186/1743-422x-7-47

Abstract

BackgroundEV71 occasionally cause a series of severe neurological symptoms, including aseptic meningitis, encephalitis, and poliomyelitis-like paralysis. However, the neurological destruction mechanism was remained to be clarified. This study described the cross reaction between EV71 induced IgG and human brain tissue.ResultsCross reaction of the IgG from 30 EV71 infected patients' sera to human tissues of cerebra was observed, which suggested that some EV71 antigens could induce IgG cross-reactivity to human cerebra. To identify the regions of EV71 virus that containing above antigens, the polypeptide of virus was divided into 19 peptides by expression in prokaryotes cell. Mouse anti-sera of these peptides was prepared and applied in immunohistochemical staining with human adult and fetus brain tissue, respectively. The result indicated the 19 peptides can be classified into three groups: strong cross-reactivity, weak cross-reactivity and no cross-reactivity with human brain tissue according the cross reaction activity. Then, the increased Blood Brain Barrier (BBB) permeability and permits IgG entry in neonatal mice after EV71 infection was determined.ConclusionEV71 induced IgG could enter BBB and cross-reacted with brain tissue in EV71 infected neonatal mice, and then the peptides of EV71 that could induce cross-reactivity with brain tissue were identified, which should be avoided in future vaccine designing.

Highlights

EV71 occasionally cause a series of severe neurological symptoms, including aseptic meningitis, encephalitis, and poliomyelitis-like paralysis
Thirty sera from children with HFMD was collected, who was infected with EV71 after RT-PCR diagnosis the specimen of throat swab, and the presence of EV71 induced antibody in all the thirty sera was verified by enzyme-linked immunosorbent assay (ELISA)
The expression and purification of the peptides disassembled from EV71To identify the regions of EV71 virus that can induce antibodies binding with human brain tissue, the genome of EV71 was divided into 22 regions in sequence, which encode peptides between 22~156 amino acids (Fig. 2A), and the nearby fragments in a functional gene have 12 to 39 bp overlap to avoid the miss of epitope

Summary

Introduction

EV71 occasionally cause a series of severe neurological symptoms, including aseptic meningitis, encephalitis, and poliomyelitis-like paralysis. This study described the cross reaction between EV71 induced IgG and human brain tissue. EV71 virus infection was reported to increase the permeability of BBB [20,21]. As enter of virus into cranial was dependent on a retrograde axonal neuronal transmission way, the increased permeability in BBB was presumed not essential for virus through BBB. As described in Epilepsy, self immunity caused by the common antigens between virus and cell receptors lead to neuron injury, in which the central nervous system (CNS) is attacked by the immune system and that provide a inspiration for the possible new way during the pathology of EV71 infection study [22]

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Results

Discussion

Conclusion