CHRONIC VIRAL INFECTIONS--MOLECULAR BIOLOGY OF HUMAN JC VIRUS

近年来，对该病发病机制的认识取得了一定进展， 进行性多灶性白质脑病（PML），一种亚急性 由少突胶质细胞感染引起的脱髓鞘疾病 JC病毒（JCV） DNA：DNA原位杂交的应用 骨髓单个核细胞的JCV感染 脾脏是病毒潜伏的重要部位， 病毒扩散到大脑。 免疫细胞化学测定具有 鉴定出单核细胞是B淋巴细胞。 此外，JCV 感染的单核细胞被发现在Virchow-Robin间隙， 这强烈暗示了淋巴细胞的参与 在疾病从系统潜伏期发展到致病状态中 中枢神经系统（CNS）。 为了解释JCV独特的生物学特性，深入研究了 对调控区内病毒基因组的分析表明， 一种不寻常的DNA结构 S1核酸酶图谱和 溴乙醛修饰检测TATA中的敏感位点 盒接近DNA复制的起点。 这些结果 表明调控区含有非B，但右手 DNA构象，其重要性可能反映了 基因表达的调控。 对发育神经生物学的兴趣日益增长， 试剂的可用性导致了对大胶质细胞的研究 在支持JC病毒的人胎脑培养物中， 乘法 短期和细胞的细胞成分 7 - 16周胎龄人脑的悬浮培养物 利用神经胶质细胞类型特异性标记进行比较。 在 与早期大鼠CNS的报道相反，人胎儿神经胶质细胞 第二型在第一型之前出现 神经胶质细胞 这些结果表明， 表型相似细胞的发育年表， 老鼠和人类的神经系统

Progress has been made in the understanding of the pathogenesis of progressive multifocal leukoencephalopathy (PML), a subacute demyelinating disease resulting from infection of oligodendrocytes by JC virus (JCV). The use of DNA:DNA in situ hybridization has implicated JCV infection of mononuclear cells of the bone marrow and spleen as an important site for viral latency and probable spread of the virus to the brain. Immunocytochemical assays have identified the monoclear cells as B-lymphocytes. Furthermore, JCV infected monoclear cells were found in the Virchow-Robin spaces of the brain, which strongly suggests the involvement of lymphocytes in disease progression from systemic latency to a pathogenic state within the central nervous system (CNS). To account for the unique biological properties of JCV, an in-depth analysis of the viral genome within the regulatory region indicated an unusual DNA structure. S1 nuclease mapping and bromoacetaldehyde modification detected sensitive sites in the TATA box proximal to the origin of DNA replication. These results indicated the regulatory region contained non-B, but right handed DNA conformations, whose significance may reflect a role in the regulation of gene expression. The growing interest in developmental neurobiology and the availability of reagents has led to a study of the macroglial cells in human fetal brain cultures which support JC virus multiplication. Cellular compositions of short-term and cell suspension cultures of human brain from fetal ages 7 to 16 weeks were compared utilizing glial cell type-specific markers. In contrast to reports on the early rat CNS, human fetal glial cells characterized as Type II emerged developmentally before Type 1 glial cells. These results suggest fundamental differences in the chronology of development of phenotypically similar cells found in the rat and human nervous system.