Major E O, Vacante D A
Infectious Diseases Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland 20892.
J Neuropathol Exp Neurol. 1989 Jul;48(4):425-36. doi: 10.1097/00005072-198907000-00004.
JC virus (JCV) has frequently been described as a tissue specific agent in the human population targeting the myelin producing oligodendrocyte whose destruction results in the demyelinating disease, progressive multifocal leukoencephalopathy (PML). JC virus growth in cell culture systems has generally reflected that observation because its multiplication is most efficient in cultures derived from human fetal brain. These cultures, however, are composed of a mixed population of cells phenotypically categorized as either astrocytes or precursors to oligodendrocytes. We have been able to separate mixed populations of glial cells from human fetal brain in culture and produce a pure population of astrocytes. We then analyzed the astrocyte cell cultures for their ability to support JCV transcription, replication, and virion production. Our results demonstrate that cultures of astrocytic cell types support JCV gene expression leading to virus multiplication. These astrocytic cell cultures also can be passaged several times in culture without loss of their astrocytic phenotypes or susceptibility to JCV infection. These data are consistent with our studies of JCV gene expression in fixed brain tissues of PML patients and virus immortalized astrocytic cell lines. These results strongly suggest that astrocytes as well as oligodendrocytes play a role in the pathogenesis of PML and should focus additional experiments on this particular cell type.
JC病毒（JCV）在人类中常被描述为一种组织特异性病原体，其靶向产生髓磷脂的少突胶质细胞，该细胞的破坏会导致脱髓鞘疾病——进行性多灶性白质脑病（PML）。JC病毒在细胞培养系统中的生长情况通常反映了这一观察结果，因为它在源自人类胎儿大脑的培养物中增殖效率最高。然而，这些培养物由表型分类为星形胶质细胞或少突胶质细胞前体的混合细胞群体组成。我们已经能够从培养的人类胎儿大脑中分离出胶质细胞的混合群体，并产生纯的星形胶质细胞群体。然后，我们分析了星形胶质细胞培养物支持JCV转录、复制和病毒粒子产生的能力。我们的结果表明，星形胶质细胞类型的培养物支持JCV基因表达，从而导致病毒增殖。这些星形胶质细胞培养物在培养中也可以传代几次，而不会丧失其星形胶质细胞表型或对JCV感染的易感性。这些数据与我们对PML患者固定脑组织和病毒永生化星形胶质细胞系中JCV基因表达的研究一致。这些结果强烈表明，星形胶质细胞和少突胶质细胞在PML的发病机制中都发挥了作用，并且应该将更多实验聚焦于这种特定的细胞类型。
