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JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy
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Author(s)
Corbridge, Sarah M.
Rice, Richard C.
Bean, Linda A.
Wüthrich, Christian
Dang, Xin
Nicholson, Daniel A.
Koralnik, Igor J.
Date Issued
April 2019
Journal
Journal of NeuroVirology
Publisher
Springer Science and Business Media LLC
Citation
Corbridge, Sarah M. et al. "JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy." Journal of NeuroVirology 25, 4 (April 2019): 520–524. © 2019 Journal of NeuroVirology, Inc
Version
Author's final manuscript
Abstract
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.
MIT Department
McGovern Institute for Brain Research at MIT
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DOI of Published Version
https://doi.org/10.1007/s13365-019-00753-y
