Jordan C A, Friedrich V L, Godfraind C, Cardellechio C B, Holmes K V, Dubois-Dalcq M
Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
Glia. 1989;2(5):318-29. doi: 10.1002/glia.440020505.
C57BI/6N mice develop a CNS demyelinating disease when inoculated intracranially at 4 weeks of age with the A59 strain of mouse hepatitis virus (MHV-A59). In order to explore the virus-host interactions, the histological features of the demyelinating disease were correlated with the spatial and temporal distribution of viral transcripts and the expression of oligodendrocyte-specific genes (myelin basic protein, proteolipid protein, myelin-associated glycoprotein, and 2',3' cyclic nucleotide 3'-phosphohydrolase) in the spinal cord of diseased mice. Three distinct phases in the disease were identified. In the first phase, 1 week postinfection (1 WPI), virus replication was widespread in both gray and white matter but was preferentially occurring in glial cells. In the ventral and dorsal root zones where viral transcripts were most abundant, all myelin gene transcripts were decreased before demyelination was seen. During the second phase of the disease (2-3 WPI), viral transcripts decreased in abundance and became restricted to the white matter. Numerous demyelinating lesions were observed and were characterized by inflammatory cells, paucity of oligodendrocytes, and a profound decrease of all myelin gene transcripts. In the third phase of the disease (4-6 WPI) no viral transcripts were detected, and remyelination began. In the lesions and the tissue surrounding them, transcripts of all myelin genes increased to levels above normal. The increased expression of myelin gene transcripts occurred in a synchronized manner and with a cellular distribution reminiscent of that seen in developmental myelination. These molecular events correlated with efficient remyelination and clinical recovery in this murine demyelinating disease.
4周龄的C57BI/6N小鼠经颅内接种小鼠肝炎病毒A59株（MHV - A59）后会发生中枢神经系统脱髓鞘疾病。为了探究病毒与宿主的相互作用，将脱髓鞘疾病的组织学特征与患病小鼠脊髓中病毒转录本的时空分布以及少突胶质细胞特异性基因（髓鞘碱性蛋白、蛋白脂蛋白、髓鞘相关糖蛋白和2',3' - 环核苷酸3'-磷酸水解酶）的表达进行了关联分析。确定了疾病的三个不同阶段。在第一阶段，感染后1周（1 WPI），病毒复制在灰质和白质中广泛存在，但优先发生在神经胶质细胞中。在病毒转录本最丰富的腹侧和背根区域，在出现脱髓鞘之前，所有髓鞘基因转录本均减少。在疾病的第二阶段（2 - 3 WPI），病毒转录本丰度降低并局限于白质。观察到许多脱髓鞘病变，其特征为炎症细胞、少突胶质细胞数量稀少以及所有髓鞘基因转录本显著减少。在疾病的第三阶段（4 - 6 WPI），未检测到病毒转录本，并且开始了髓鞘再生。在病变及其周围组织中，所有髓鞘基因的转录本增加到高于正常水平。髓鞘基因转录本的表达增加以同步方式发生，并且细胞分布让人联想到发育性髓鞘形成过程中所见的情况。这些分子事件与这种小鼠脱髓鞘疾病中的有效髓鞘再生和临床恢复相关。
