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柯萨奇病毒诱导的急性新生儿中枢神经系统疾病模型

Coxsackievirus-induced acute neonatal central nervous system disease model.

作者信息

Wang Lulu, Dong Changyuan, Chen Dong-E, Song Zhen

机构信息

Laboratory of Molecular Virus & Cancer, State Key Laboratory of Virology, Wuhan University School of BasicMedicine Wuhan 430071, China.

Department of Epidemiology and Biostatistics, Wuhan University School of Public Health Wuhan 430071, China.

出版信息

Int J Clin Exp Pathol. 2014 Feb 15;7(3):858-69. eCollection 2014.

Abstract

Coxsackievirus B (CVB) is a significant pathogen that causes pediatric central nervous system disease with acute syndromes commonly. The onset of its infection was abrupt, and after recovery there usually will be severe mental sequelae. The disease model for research was not established by the way of natural infection, although there are various investigations about the CVB-induced central nervous system (CNS) diseases. Thus, we have established an acute neonatal CNS disease mice model by CVB orally infecting. This model imitated the natural infection route and focuses the onset of CNS disease, inducing severe infection and lesion in the hippocampus and cortex regions, and the stability of the model was demonstrated. A pathology score system was developed for quantitative pathology analysis, which standardizes the CNS pathology analysis by statistics analysis. By this model, the track of CVB penetrating the blood brain barrier in vivo has been captured. One of the experimental strains CVB3/Macocy, as a new variant, was isolated, and its genomic RNA was cloned. According to its nucleotide sequence, we have characterized its genomic structure and defined its genotype. Based on the sequence, some mutations which do not change the CVB-induced CNS damage have been found. The model is an effective tool for studies on CVB-induced CNS diseases.

摘要

柯萨奇病毒B(CVB)是一种重要的病原体,常引发小儿中枢神经系统急性综合征疾病。其感染发病突然,康复后通常会留下严重的精神后遗症。尽管对CVB诱导的中枢神经系统(CNS)疾病有各种研究,但尚未通过自然感染的方式建立用于研究的疾病模型。因此,我们通过口服感染CVB建立了急性新生儿中枢神经系统疾病小鼠模型。该模型模拟了自然感染途径,聚焦于中枢神经系统疾病的发病,在海马体和皮质区域引发严重感染和病变,并证明了模型的稳定性。开发了一种病理评分系统用于定量病理分析,通过统计分析使中枢神经系统病理分析标准化。通过该模型,捕捉到了CVB在体内穿透血脑屏障的轨迹。分离出了实验菌株之一CVB3/Macocy作为新变种,并克隆了其基因组RNA。根据其核苷酸序列,我们对其基因组结构进行了表征并确定了其基因型。基于该序列,发现了一些不改变CVB诱导的中枢神经系统损伤的突变。该模型是研究CVB诱导的中枢神经系统疾病的有效工具。

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