JC VIRUS-DNA IS PRESENT IN MANY HUMAN BRAIN SAMPLES FROM PATIENTS WITHOUT PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
JC VIRUS-DNA IS PRESENT IN MANY HUMAN BRAIN SAMPLES FROM PATIENTS WITHOUT PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
复制标题
DOI：
10.1128/jvi.66.10.5726-5734.1992
复制
发表时间：
1992-10-01
影响因子：
5.4
通讯作者：
FRISQUE, RJ
中科院分区：
文献类型：
--
作者：
WHITE, FA;ISHAQ, M;FRISQUE, RJ
应用聚合酶链反应对正常和病变脑组织和肾组织切片进行JC病毒（JCV）DNA筛查。正如预期的那样，当使用多种JCV特异性引物和探针组合时，从进行性多灶性白质脑病（PML）患者中获得的所有样本均检测为阳性。出乎意料的是，超过50%的非PML受影响的大脑也被发现含有低水平的JCV DNA。为了确认在组织切片中观察到的阳性信号不是污染的结果，对扩增的DNA进行克隆和测序，在某些情况下显示代表先前未鉴定的JCV菌株。已在人类宿主中检测到JCV的两种主要调控区构型：原型JCV，其在正常和免疫受损个体的尿液中排泄，以及在患病脑中发现的“PML型”JCV。后一组变体似乎通过启动子-增强子区域内序列的缺失和复制而衍生自原型JCV。在本研究中，JCV的原型菌株仅在正常肾脏样本中鉴定;在非PML影响的脑标本和PML患者的肾组织中发现的JCV DNA与从PML影响的脑组织中分离的菌株相似。我们的研究结果表明，JCV到达大脑的频率比以前认为的更高，并且可能在该部位持续存在而不会引起脱髓鞘疾病。随后的长期免疫缺陷发作或与免疫妥协剂的直接相互作用（例如，人类免疫缺陷病毒1型（HIV-1）可能激活潜伏的JCV感染并导致PML的发展。
Sections of normal and diseased brain and kidney tissues were screened for the presence of JC virus (JCV) DNA by using the polymerase chain reaction. As expected, all samples obtained from patients with progressive multifocal leukoencephalopathy (PML) tested positive when multiple JCV-specific primer and probe combinations were used. Unexpectedly, more than 50% of non-PML-affected brains were also found to harbor low levels of JCV DNA. To confirm that the positive signals seen in the tissue sections were not the result of contamination, amplified DNA was cloned and sequenced and in some cases was shown to represent strains of JCV not identified previously. Two predominant regulatory region configurations of JCV have been detected in the human host: archetype JCV, which is excreted in the urine of normal and immunocompromised individuals, and "PML-type" JCV found in diseased brains. This latter group of variants appears to derive from archetype JCV by the deletion and duplication of sequences within the promoter-enhancer region. In the present study, the archetype strain of JCV was identified only in normal kidney samples; JCV DNA found in non-PML-affected brain specimens and in kidney tissue from patients with PML resembled that of strains isolated from PML-affected brain tissue. Our findings indicate that JCV reaches the brain more frequently than previously thought and may persist at this site without causing demyelinating disease. A subsequent episode of prolonged immunodeficiency or a direct interaction with an immunocompromising agent (e.g., human immunodeficiency virus type 1) might activate the latent JCV infection and lead to the development of PML.