Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Boston, MA, USA.
J Neurovirol. 2019 Aug;25(4):520-524. doi: 10.1007/s13365-019-00753-y. Epub 2019 Apr 25.
JC virus (JCV) can cause a lytic infection of oligodendrocytes and astrocytes in the central nervous system (CNS) leading to progressive multifocal leukoencephalopathy (PML). JCV can also infect meningeal and choroid plexus cells causing JCV meningitis (JCVM). Whether JCV also infects meningeal and choroid plexus cells in PML patients and other immunosuppressed individuals with no overt symptoms of meningitis remains unknown. We therefore analyzed archival formalin-fixed, paraffin-embedded brain samples from PML patients, and HIV-seropositive and seronegative control subjects by immunohistochemistry for the presence of JCV early regulatory T Ag and JCV VP1 late capsid protein. In meninges, we detected JCV T Ag in 11/48 (22.9%) and JCV VP1 protein in 8/48 (16.7%) PML patients. In choroid plexi, we detected JCV T Ag in 1/7 (14.2%) and JCV VP1 protein in 1/8 (12.5%) PML patients. Neither JCV T Ag nor VP1 protein could be detected in meninges or choroid plexus of HIV-seropositive and HIV-seronegative control subjects without PML. In addition, examination of underlying cerebellar cortex of PML patients revealed JCV-infected cells in the molecular layer, including GAD 67+ interneurons, but not in HIV-seropositive and HIV-seronegative control subjects without PML. Our findings suggest that productive JCV infection of meningeal cells and choroid plexus cells also occurs in PML patients without signs or symptoms of meningitis. The phenotypic characterization of JCV-infected neurons in the molecular layer deserves further study. This data provides new insight into JCV pathogenesis in the CNS.
JC 病毒（JCV）可引起中枢神经系统（CNS）中少突胶质细胞和星形胶质细胞的裂解感染，导致进行性多灶性白质脑病（PML）。JCV 还可以感染脑膜和脉络丛细胞，导致 JCV 脑膜炎（JCVM）。JCV 是否也感染 PML 患者和其他无明显脑膜炎症状的免疫抑制个体的脑膜和脉络丛细胞尚不清楚。因此，我们通过免疫组织化学法分析了来自 PML 患者、HIV 血清阳性和血清阴性对照者的存档福尔马林固定、石蜡包埋的脑组织样本，以检测 JCV 早期调节 T 抗原和 JCV VP1 晚期衣壳蛋白的存在。在脑膜中，我们在 11/48（22.9%）例 PML 患者中检测到 JCV TAg，在 8/48（16.7%）例 PML 患者中检测到 JCV VP1 蛋白。在脉络丛中，我们在 1/7（14.2%）例 PML 患者中检测到 JCV TAg，在 1/8（12.5%）例 PML 患者中检测到 JCV VP1 蛋白。在没有 PML 的 HIV 血清阳性和血清阴性对照者的脑膜或脉络丛中，均未检测到 JCV TAg 或 VP1 蛋白。此外，对 PML 患者小脑皮质的检查显示，分子层中有 JCV 感染的细胞，包括 GAD67+中间神经元，但在没有 PML 的 HIV 血清阳性和血清阴性对照者中没有。我们的研究结果表明，在没有脑膜炎症状或体征的 PML 患者中，脑膜细胞和脉络丛细胞也发生了 JCV 的复制性感染。分子层中 JCV 感染神经元的表型特征值得进一步研究。该数据为 JCV 在中枢神经系统中的发病机制提供了新的见解。
