RESTRICTED INFECTION WITH CANINE-DISTEMPER VIRUS LEADS TO DOWN-REGULATION OF MYELIN GENE-TRANSCRIPTION IN CULTURED OLIGODENDROCYTES
RESTRICTED INFECTION WITH CANINE-DISTEMPER VIRUS LEADS TO DOWN-REGULATION OF MYELIN GENE-TRANSCRIPTION IN CULTURED OLIGODENDROCYTES
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DOI：
10.1007/bf00296516
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发表时间：
1995-09-01
影响因子：
12.7
通讯作者：
ZURBRIGGEN, A
中科院分区：
文献类型：
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作者：
GRABER, HU;MULLER, CF;ZURBRIGGEN, A
犬瘟热病毒（CDV）可引起中枢神经系统少突胶质细胞变性和多灶性脱髓鞘。少突胶质细胞变性的机制尚不清楚，但已显示这些细胞的有限感染没有病毒蛋白质产生。使用免疫细胞化学和原位杂交的组合，我们能够证明在整个观察期间（感染后7-35天），在少突胶质细胞中的CDV感染的脑细胞培养物的整个病毒基因组的转录。因此，病毒蛋白和颗粒产生的缺乏不能基于有缺陷的病毒转录来解释。本研究还表明，少突胶质细胞与CDV的限制性感染下调的主要髓鞘基因编码的蛋白脂质蛋白，髓鞘碱性蛋白（MBP）和髓鞘相关糖蛋白的转录以非常相似的方式。在正常和感染的少突胶质细胞群体中使用MBP原位杂交产物的光密度测定法，可以观察到形态学变化之前很久的效果。本研究结果强烈表明，犬瘟热脱髓鞘是由少突胶质细胞的限制性CDV感染引起的，其下调了多种细胞基因的表达，特别是那些编码髓鞘蛋白的基因。因此，受感染的细胞不再能够合成维持其结构完整性所必需的所有膜化合物。
Canine distemper virus (CDV) induces oligodendroglial degeneration and multifocal demyelination in the central nervous system. The mechanism of oligodendrocyte degeneration is not understood but it has been shown that there is a restricted infection of these cells without viral protein production. Using a combination of immunocytochemistry and in situ hybridization we were able to demonstrate the transcription of the entire virus genome throughout the whole observation period (7-35 days after infection) in oligodendrocytes in CDV-infected brain cell cultures. Therefore, the lack of viral protein and particle production can not be explained on the basis of a defective viral transcription. The present study also shows that a restricted infection of oligodendrocytes with CDV down-regulates the transcription of the major myelin genes coding for proteolipid protein, myelin basic protein (MBP) and myelin-associated glycoprotein in a very similar way. Using densitometry for in situ hybridization products of MBP in populations of normal and infected oligodendrocytes, an effect could be observed long before morphological changes were detectable. The present results strongly suggest that demyelination in distemper is induced by a restricted CDV infection of oligodendrocytes which down-regulates the expression of a variety of cellular genes, in particular those coding for myelin proteins. Consequently, the infected cells are no longer able to synthesize all the membrane compounds which are necessary for maintaining their structural integrity.