CHRONIC VIRAL INFECTIONS--MOLECULAR BIOLOGY OF HUMAN JC VIRUS

我们目前的结果强调了分子间的相互作用， JC病毒（JCV）与人脑神经胶质细胞。 进展 了解JCV感染的进展 导致中枢神经系统脱髓鞘 免疫缺陷患者。 在分子水平上我们发现 JCV早期基因转录受胶质细胞调控 识别JCV中DNA序列的特定蛋白质 监管区域。 相反，JCV DNA复制受到调控， 在灵长类动物中发现的特定蛋白质 细胞 我们已经提供了进一步的证据， 原位DNA：DNA杂交作为实验室诊断 患者脑活检标本中存在JCV DNA 进行性多灶性白质脑病（PML）。 临床检查、组织病理学和电镜 在所有情况下，鉴定与阳性杂交相关 结果，从而表明杂交试验能够 确定JCV是PML的原因。 此外，来自 分离出一例PML，其DNA部分 测序 分离的病毒被鉴定为Mad-4株， JCV。 从我们持续的动物研究中，一只可移植的猫头鹰 在培养物中发现猴星形细胞瘤释放感染性 JC病毒 培养中只有30%的活肿瘤细胞 释放的病毒表明建立了一个持久的 载体培养 被命名为JCV 586的释放病毒是 通过DNA测序发现，在DNA序列中含有19 bp的缺失。 病毒调控区的第二个串联重复序列，因此 确认病毒为Mad-4病毒株 与我们的结果相反 对于JCV Mad-1株，JCV 586 T蛋白结合宿主 细胞p53蛋白（一种核癌基因）。 此外，委员会认为， 在氨基末端结合表位的单克隆抗体 和SV 40 T蛋白的羧基末端，也识别 JCV 586 T蛋白，表明具有一定的结构同源性 JCV 586和SV 40 T蛋白之间的差异。

Our current results emphasize the molecular interactions of the JC virus (JCV) with glial cells of the human brain. Progress has been made in understanding the progression of the JCV infection which leads to a demyelination of the central nervous system of immunodeficient patients. At the molecular level we have found that JCV early gene transcription is regulated by glial cell specific proteins which recognize the DNA sequences in the JCV regulatory region. In contrast, JCV DNA replication is regulated by specific proteins which are found in a wide range of primate cells. We have provided further evidence of the accuracy of in situ DNA:DNA hyridization as a laboratory diagnosis for the presence of JCV DNA in brain biopsy specimens from patients with progressive multifocal leuko-encephalopathy (PML). Clinical examinations, histopathology and electron microscopic identification correlated in all cases to positive hybridization results, thus indicating that hybridization tests are able to identify JCV as the cause of PML. Furthermore, viral DNA from a case study of PML was isolated and its DNA partially sequenced. The isolated virus was identified as a Mad-4 strain of JCV. From our continuing animal studies, a transplantable owl monkey astrocytoma was found in culture to release infectious JC virus. Only about 30% of the viable tumor cells in culture released virus indicating the establishment of a persistent carrier culture. The released virus designated JCV 586 was found by DNA sequencing to contain a 19 bp deletion in the second tandem repeat of the viral regulatory region, thus identifying the virus as a Mad-4 strain. In contrast to our results with the JCV Mad-1 strain, the JCV 586 T protein binds the host cellular p53 protein (a nuclear oncogene). Furthermore, monoclonal antibodies which bind epitopes at the amino terminus and the carboxy terminus of the SV 40 T protein, also recognize the JCV 586 T protein, indicating some structural homology between the JCV 586 and SV 40 T proteins.