Rearrangement of the JC virus regulatory region sequence in the bone marrow of a patient with rheumatoid arthritis and progressive multifocal leukoencephalopathy

Angela Marzocchetti; Christian Wuthrich; Chen S Tan; Troy Tompkins; Francisco Bernal-Cano; Parul Bhargava; Allan H Ropper; Igor J Koralnik

doi:10.1080/13550280802356837

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Rearrangement of the JC virus regulatory region sequence in the bone marrow of a patient with rheumatoid arthritis and progressive multifocal leukoencephalopathy

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Rearrangement of the JC virus regulatory region sequence in the bone marrow of a patient with rheumatoid arthritis and progressive multifocal leukoencephalopathy

Angela Marzocchetti, Christian Wuthrich, Chen S Tan, Troy Tompkins, Francisco Bernal-Cano, Parul Bhargava, Allan H Ropper and Igor J Koralnik

Journal of neurovirology, Vol.14(5), pp.455-458

2008

DOI: 10.1080/13550280802356837

PMCID: PMC2643300

PMID: 18989816

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https://www.ncbi.nlm.nih.gov/pmc/articles/2643300View

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Abstract

The polyomavirus JC (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy (PML). JCV remains quiescent in kidneys, where it displays a stable archetypal regulatory region (RR). Conversely, rearranged JCV RR, including tandem repeat patterns found in the central nervous system (CNS) of PML patients, have been associated with neurovirulence. The precise site and mechanism of JCV RR transformation is unknown. We present herein a patient with rheumatoid arthritis treated with methotrexate, who developed PML and had a rapid fatal outcome. JCV DNA polymerase chain reaction (PCR) was positive in cerebrospinal fluid (CSF), bone marrow, blood, and urine. Double-immunohistochemical staining demonstrated that 9% of bone marrow CD138+ plasma cells sustained productive infection by JCV, accounting for 94% of JCV-infected cells. JCV RR analysis revealed archetype and rearranged RR forms in bone marrow, whereas RR with tandem repeat was predominant in blood. These results suggest that the bone marrow may be a potential site of JCV pathogenic transformation. Further studies will be needed to determine the prevalence of JCV in bone marrow of immunosuppressed individuals at risk of PML and characterize the RR and phenotype of these JCV isolates.

Details

Title: Subtitle: Rearrangement of the JC virus regulatory region sequence in the bone marrow of a patient with rheumatoid arthritis and progressive multifocal leukoencephalopathy
Creators: Angela Marzocchetti - Beth Israel Deaconess Medical Center
Christian Wuthrich - Beth Israel Deaconess Medical Center
Chen S Tan - Beth Israel Deaconess Medical Center
Troy Tompkins - Beth Israel Deaconess Medical Center
Francisco Bernal-Cano - Beth Israel Deaconess Medical Center
Parul Bhargava - Beth Israel Deaconess Medical Center
Allan H Ropper - Brigham and Women's Hospital
Igor J Koralnik - Beth Israel Deaconess Medical Center
Resource Type: Journal article
Publication Details: Journal of neurovirology, Vol.14(5), pp.455-458
DOI: 10.1080/13550280802356837
PMID: 18989816
PMCID: PMC2643300
NLM abbreviation: J Neurovirol
ISSN: 1355-0284
eISSN: 1538-2443
Publisher: Informa UK Ltd
Language: English
Date published: 2008
Academic Unit: Iowa Neuroscience Institute; Internal Medicine
Record Identifier: 9984366374602771

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