JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy

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...

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Main Authors: Corbridge, Sarah M., Rice, Richard C., Bean, Linda A., Wüthrich, Christian, Dang, Xin, Nicholson, Daniel A., Koralnik, Igor J.
Other Authors: McGovern Institute for Brain Research at MIT
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2021
Online Access:https://hdl.handle.net/1721.1/131279
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author Corbridge, Sarah M.
Rice, Richard C.
Bean, Linda A.
Wüthrich, Christian
Dang, Xin
Nicholson, Daniel A.
Koralnik, Igor J.
author2 McGovern Institute for Brain Research at MIT
author_facet McGovern Institute for Brain Research at MIT
Corbridge, Sarah M.
Rice, Richard C.
Bean, Linda A.
Wüthrich, Christian
Dang, Xin
Nicholson, Daniel A.
Koralnik, Igor J.
author_sort Corbridge, Sarah M.
collection MIT
description 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.
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spelling mit-1721.1/1312792021-09-20T17:19:14Z JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy Corbridge, Sarah M. Rice, Richard C. Bean, Linda A. Wüthrich, Christian Dang, Xin Nicholson, Daniel A. Koralnik, Igor J. McGovern Institute for Brain Research at MIT 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. 2021-09-16T18:37:49Z 2021-09-16T18:37:49Z 2019-04 2018-12 2020-09-24T21:16:17Z Article http://purl.org/eprint/type/JournalArticle 1355-0284 1538-2443 https://hdl.handle.net/1721.1/131279 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 en https://doi.org/10.1007/s13365-019-00753-y Journal of NeuroVirology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. Journal of NeuroVirology, Inc. application/pdf Springer Science and Business Media LLC Springer International Publishing
spellingShingle Corbridge, Sarah M.
Rice, Richard C.
Bean, Linda A.
Wüthrich, Christian
Dang, Xin
Nicholson, Daniel A.
Koralnik, Igor J.
JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy
title JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy
title_full JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy
title_fullStr JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy
title_full_unstemmed JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy
title_short JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy
title_sort jc virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy
url https://hdl.handle.net/1721.1/131279
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