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新生期感染博尔纳病病毒的沙鼠大脑中的神经疾病与病毒动态

Neurological diseases and viral dynamics in the brains of neonatally borna disease virus-infected gerbils.

作者信息

Watanabe M, Lee B J, Kamitani W, Kobayashi T, Taniyama H, Tomonaga K, Ikuta K

机构信息

Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.

出版信息

Virology. 2001 Mar 30;282(1):65-76. doi: 10.1006/viro.2001.0813.

DOI:10.1006/viro.2001.0813
PMID:11259191
Abstract

Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that causes a chronic neurological disease in a wide variety of animal species. To develop a better understanding of the correlation between neurological disorders caused by BDV infection and virus distribution in the brain, we investigated viral dynamics in the central nervous system (CNS) of neonatally BDV-infected gerbils during the late stage of infection. Despite the severe symptoms and aggressive proliferation of BDV in the infected gerbils, no apparent neuroanatomical abnormalities or neuronal cell loss was observed in the infected gerbil brain. Furthermore, no or only minimal infiltration was observed in the infected gerbil brain. By in situ hybridization and real-time PCR analyses, we demonstrated that the predominant area of expression of BDV mRNA, as well as the protein, was shifted in the brain in association with progression of disease. In nondiseased gerbils, the virus replication was predominantly detected in the cerebral cortex and hippocampus of the CNS. On the other hand, diseased animals showed a high level of expression in the lower brain stem and cerebellum, especially in Purkinje cell neurons. These observations suggested that significant replication of the virus in specific areas of the CNS is critical for development of the neurological disorders in BDV-infected neonatal gerbils.

摘要

博尔纳病病毒(BDV)是一种非细胞溶解性嗜神经RNA病毒,可在多种动物物种中引发慢性神经疾病。为了更好地理解BDV感染所致神经紊乱与病毒在脑中分布之间的关联,我们研究了新生期感染BDV的沙鼠在感染后期中枢神经系统(CNS)中的病毒动态。尽管感染的沙鼠出现了严重症状且BDV大量增殖,但在感染沙鼠的脑中未观察到明显的神经解剖学异常或神经元细胞损失。此外,在感染沙鼠的脑中未观察到或仅观察到极少的浸润现象。通过原位杂交和实时PCR分析,我们证明,随着疾病进展,BDV mRNA以及蛋白质的主要表达区域在脑中发生了转移。在未患病的沙鼠中,主要在CNS的大脑皮层和海马体中检测到病毒复制。另一方面,患病动物在脑桥下部和小脑,尤其是浦肯野细胞神经元中表现出高水平表达。这些观察结果表明,病毒在CNS特定区域的大量复制对于感染BDV的新生沙鼠神经紊乱的发展至关重要。

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