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无毒力狂犬病病毒变异株Av01在小鼠脑立体定位接种时的神经毒力基础

Basis of neurovirulence of avirulent rabies virus variant Av01 with stereotaxic brain inoculation in mice.

作者信息

Yang C, Jackson A C

机构信息

Department of Medicine, Queen's University, Kingston, Ontario, Canada.

出版信息

J Gen Virol. 1992 Apr;73 ( Pt 4):895-900. doi: 10.1099/0022-1317-73-4-895.

DOI:10.1099/0022-1317-73-4-895
PMID:1634878
Abstract

Av01 is a variant of the challenge virus standard strain of fixed rabies virus that was selected with a neutralizing anti-glycoprotein monoclonal antibody, and has a single amino acid change in the glycoprotein. It is avirulent after both intracerebral and peripheral routes of inoculation in adult mice. In this study, Av01 was found to be neurovirulent with stereotaxic brain inoculation in either the striatum or cerebellum of adult mice. Mice that had been inoculated simultaneously with Av01 by the intracerebral and intrastriatal routes recovered. More infectious virus was present in the brains of mice inoculated intrastriatally than intracerebrally, and more neurons contained rabies virus antigen. However, the topographical distribution of infected neurons was similar with both routes. Serum neutralizing antibodies against rabies virus were produced later and in smaller quantities after intrastriatal inoculation. Av01 is probably neurovirulent after stereotaxic brain inoculation because this route produces both a direct site of viral entry into the central nervous system and a low level of immune stimulation.

摘要

Av01是固定狂犬病病毒标准攻击毒株的一个变种,它是用一种中和抗糖蛋白单克隆抗体筛选出来的,其糖蛋白中有一个氨基酸发生了变化。在成年小鼠中,经脑内和外周途径接种后它都没有致病性。在本研究中,发现Av01经立体定向脑内接种于成年小鼠的纹状体或小脑时具有神经毒性。通过脑内和纹状体内途径同时接种Av01的小鼠恢复了健康。纹状体内接种的小鼠脑中存在的感染性病毒比脑内接种的更多,并且更多的神经元含有狂犬病病毒抗原。然而,两种途径感染神经元的拓扑分布是相似的。纹状体内接种后,针对狂犬病病毒的血清中和抗体产生得更晚且数量更少。Av01经立体定向脑内接种后可能具有神经毒性,因为这种途径既产生了病毒进入中枢神经系统的直接位点,又产生了低水平的免疫刺激。

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The rabies virus glycoprotein determines the distribution of different rabies virus strains in the brain.
狂犬病病毒糖蛋白决定了不同狂犬病病毒株在大脑中的分布。
J Neurovirol. 2002 Aug;8(4):345-52. doi: 10.1080/13550280290100707.
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Pathogenicity of different rabies virus variants inversely correlates with apoptosis and rabies virus glycoprotein expression in infected primary neuron cultures.在感染的原代神经元培养物中,不同狂犬病毒变体的致病性与细胞凋亡及狂犬病毒糖蛋白表达呈负相关。
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