The HHV6 paradox: ubiquitous commensal or insidious pathogen? A two-step in situ PCR approach
The HHV6 paradox: ubiquitous commensal or insidious pathogen? A two-step in situ PCR approach
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DOI：
10.1016/s1386-6532(99)00084-0
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发表时间：
2000-05-01
影响因子：
8.8
通讯作者：
Goodman, AD
中科院分区：
文献类型：
--
作者：
Blumberg, BM;Mock, DJ;Goodman, AD
背景：进行性多灶性脑白质病（PML）和多发性硬化症（MS）是中枢神经系统（CNS）的脱髓鞘性疾病。PML主要发生在艾滋病免疫受损的个体中，被认为是由JC多瘤病毒（JCV）引起的。在多发性硬化症中，怀疑是神经营养病毒引发的，但确切的病因尚不清楚。人类疱疹病毒6 （HHV6）是一种普遍存在的、共生的、通常是良性的乙型疱疹病毒。一些研究人员已经在MS斑块和血清中发现了HHV6感染的证据。我们最近证明了PML病变中含有HHV6基因组的细胞的高频率，以及JCV和HHV6对少突胶质细胞的共同感染。这提示HHV6可能是PML病因的一个辅助因素，并对其在其他脱髓鞘疾病中的作用提出了疑问。目的：了解HHV6、JCV和HIV-1感染细胞在PML、MS、AIDS和对照中枢神经系统组织中的流行程度和细胞定位，以及它们与疾病的潜在关系。研究设计：采用一种非常规、灵敏的两步原位聚合酶链反应（ISPCR）方法，在福尔马林固定石蜡包埋的档案中枢组织中扩增和检测HHV6、JCV和HIV-1基因组dna。通过ICC检测HHV6 p41和gp101、JCV大T、HIV-1 p24 gag和NEF蛋白的表达。结果：HHV6基因在PML和MS白质病变细胞中均呈高频率表达；病灶周围明显集中。HHV6主要在少突胶质细胞中发现，但也感染了神经元。在PML病变中，HHV6的表达量高于JCV，而在艾滋病中，HIV-1的表达量高于HHV6。在正常、艾滋病和其他对照脑中检测到不同数量的HHV6基因组；感染细胞的频率随患者年龄的增长而增加。结论：高浓度的HHV6基因组与PML和MS病变相关，开启了HHV6激活可能在这些脱髓鞘疾病的发病机制中发挥作用的可能性。(C) 2000 Elsevier Science B.V.版权所有
Background: Progressive multifocal leukoencephalopathy (PML) and multiple sclerosis (MS) are demyelinative diseases of the central nervous system (CNS). PML occurs mostly in individuals with AIDS-impaired immunity and is thought to be caused by JC polyoma virus (JCV). In MS a neurotrophic virus trigger is suspected, but the precise etiology remains unknown. Human herpesvirus 6 (HHV6) is a ubiquitous, commensal and usually benign beta-herpesvirus. Some researchers have found evidence for HHV6 infection in MS plaques and sera. We recently demonstrated a high frequency of cells containing HHV6 genome in PML lesions, as well as co-infection of oligodendrocytes by JCV and HHV6. This suggests that HHV6 may be a co-factor in the etiology of PML, and raises questions about its role in other demyelinative diseases. Objectives: To determine the prevalence and cellular localization of HHV6, JCV and HIV-1 infected cells in PML, MS, AIDS and control CNS tissues, and their potential relationship with disease. Study design: An unconventional, sensitive two-step in situ polymerase chain reaction (ISPCR) procedure was used to amplify and detect HHV6, JCV and HIV-1 genomic DNAs in formalin fixed, paraffin-embedded archival CNS tissues. HHV6, JCV and HIV-1 gene expression was detected by ICC for HHV6 p41 and gp101, JCV large T, and HIV-1 p24 gag and NEF proteins. Results: A high frequency of HHV6 genome was consistently detected in both PML and MS white matter lesional cells; a peri-lesional concentration was notable. HHV6 was found mainly in oligodendrocytes, but neurons were also infected. HHV6 was present in larger amounts than JCV in PML lesions, while more HIV-1 than HHV6 was present in AIDS. Variable amounts of HHV6 genome were detected in normal, AIDS and other control brains; the frequency of infected cells tended to increase with patient age. Conclusions: High concentrations of HHV6 genome in association with PML and MS lesions, open the possibility that HHV6 activation may play a role in the pathogenesis of these demyelinative diseases. (C) 2000 Elsevier Science B.V. All rights reserved.