Blumberg B M, Mock D J, Powers J M, Ito M, Assouline J G, Baker J V, Chen B, Goodman A D
VA Bio-Medical Research Institute, Building 7, East Orange VA Medical Center, 385 Tremont Avenue, East Orange, NJ, USA.
J Clin Virol. 2000 May;16(3):159-78. doi: 10.1016/s1386-6532(99)00084-0.
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.
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.
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.
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.
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.
进行性多灶性白质脑病（PML）和多发性硬化症（MS）是中枢神经系统（CNS）的脱髓鞘疾病。PML主要发生在免疫功能因艾滋病而受损的个体中，被认为是由JC多瘤病毒（JCV）引起的。在MS中，怀疑有嗜神经病毒触发因素，但确切病因仍不清楚。人类疱疹病毒6型（HHV6）是一种普遍存在的、共生且通常无害的β疱疹病毒。一些研究人员在MS斑块和血清中发现了HHV6感染的证据。我们最近在PML病变中发现了高频率的含有HHV6基因组的细胞，以及JCV和HHV6对少突胶质细胞的共同感染。这表明HHV6可能是PML病因中的一个辅助因素，并引发了关于其在其他脱髓鞘疾病中作用的疑问。
确定HHV6、JCV和HIV-1感染细胞在PML、MS、艾滋病患者及对照CNS组织中的患病率和细胞定位，以及它们与疾病的潜在关系。
采用一种非常规的、敏感的两步原位聚合酶链反应（ISPCR）方法来扩增和检测福尔马林固定、石蜡包埋的存档CNS组织中的HHV6、JCV和HIV-1基因组DNA。通过免疫细胞化学（ICC）检测HHV6 p41和gp101、JCV大T抗原以及HIV-1 p24 gag和NEF蛋白来检测HHV6、JCV和HIV-1基因表达。
在PML和MS的白质病变细胞中均持续检测到高频率的HHV6基因组；病变周围浓度显著。HHV6主要存在于少突胶质细胞中，但神经元也被感染。在PML病变中，HHV6的含量比JCV多，而在艾滋病患者中，HIV-1的含量比HHV6多。在正常、艾滋病及其他对照大脑中检测到不同数量HHV6基因组；感染细胞的频率倾向于随患者年龄增加而升高。
与PML和MS病变相关的高浓度HHV6基因组表明，HHV6激活可能在这些脱髓鞘疾病的发病机制中起作用。
