JC Virus Latency in the Brain and Extraneural Organs of Patients with and without Progressive Multifocal Leukoencephalopathy

Chen S. Tan; Laura C. Ellis; Christian Wüthrich; Long Ngo; Thomas A. Broge; Jenny Saint-Aubyn; Janice S. Miller; Igor J. Koralnik

doi:10.1128/JVI.00609-10

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JC Virus Latency in the Brain and Extraneural Organs of Patients with and without Progressive Multifocal Leukoencephalopathy

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JC Virus Latency in the Brain and Extraneural Organs of Patients with and without Progressive Multifocal Leukoencephalopathy

Chen S. Tan, Laura C. Ellis, Christian Wüthrich, Long Ngo, Thomas A. Broge, Jenny Saint-Aubyn, Janice S. Miller and Igor J. Koralnik

Journal of virology, Vol.84(18), pp.9200-9209

07/07/2010

DOI: 10.1128/JVI.00609-10

PMCID: PMC2937633

PMID: 20610709

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Abstract

JC virus (JCV) is latent in the kidneys and lymphoid organs of healthy individuals, and its reactivation in the context of immunosuppression may lead to progressive multifocal leukoencephalopathy (PML). Whether JCV is present in the brains or other organs of healthy people and in immunosuppressed patients without PML has been a matter of debate. We detected JCV large T DNA by quantitative PCR of archival brain samples of 9/24 (38%) HIV-positive PML patients, 5/18 (28%) HIV-positive individuals, and 5/19 (26%) HIV-negative individuals. In the same samples, we detected JCV regulatory region DNA by nested PCR in 6/19 (32%) HIV-positive PML patients, 2/11 (18%) HIV-positive individuals, and 3/17 (18%) HIV-negative individuals. In addition, JCV DNA was detected in some spleen, lymph node, bone, and kidney samples from the same groups. In situ hybridization data confirmed the presence of JCV DNA in the brains of patients without PML. However, JCV proteins (VP1 or T antigen) were detected mainly in the brains of 23/24 HIV-positive PML patients, in only a few kidney samples of HIV-positive patients, with or without PML, and rarely in the bones of HIV-positive patients with PML. JCV proteins were not detected in the spleen or lymph nodes in any study group. Furthermore, analysis of the JCV regulatory region sequences showed both rearranged and archetype forms in brain and extraneural organs in all three study groups. Regulatory regions contained increased variations of rearrangements correlating with immunosuppression. These results provide evidence of JCV latency in the brain prior to severe immunosuppression and suggest new paradigms in JCV latency, compartmentalization, and reactivation.

Pathogenesis and Immunity

Details

Title: Subtitle: JC Virus Latency in the Brain and Extraneural Organs of Patients with and without Progressive Multifocal Leukoencephalopathy
Creators: Chen S. Tan - Beth Israel Deaconess Medical Center
Laura C. Ellis - Beth Israel Deaconess Medical Center
Christian Wüthrich - Harvard University
Long Ngo - Harvard University
Thomas A. Broge - Harvard University
Jenny Saint-Aubyn - Harvard University
Janice S. Miller - Harvard University
Igor J. Koralnik - Harvard University
Resource Type: Journal article
Publication Details: Journal of virology, Vol.84(18), pp.9200-9209
DOI: 10.1128/JVI.00609-10
PMID: 20610709
PMCID: PMC2937633
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology (ASM)
Language: English
Date published: 07/07/2010
Academic Unit: Iowa Neuroscience Institute; Internal Medicine
Record Identifier: 9984366283202771

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