Detection of JC Virus-Specific Immune Responses in a Novel Humanized Mouse Model

Chen Sabrina Tan; Thomas A. Broge; Edward Seung; Vlad Vrbanac; Raphael Viscidi; Jennifer Gordon; Andrew M. Tager; Igor J. Koralnik

doi:10.1371/journal.pone.0064313

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Detection of JC Virus-Specific Immune Responses in a Novel Humanized Mouse Model

Journal article

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Detection of JC Virus-Specific Immune Responses in a Novel Humanized Mouse Model

Chen Sabrina Tan, Thomas A. Broge, Edward Seung, Vlad Vrbanac, Raphael Viscidi, Jennifer Gordon, Andrew M. Tager and Igor J. Koralnik

PloS one, Vol.8(6), pp.e64313-e64313

05/20/2013

DOI: 10.1371/journal.pone.0064313

PMCID: PMC3658964

PMID: 23700470

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Abstract

Progressive Multifocal Leukoencephalopathy (PML) is an often fatal disease caused by the reactivation of the JC virus (JCV). Better understanding of viral-host interactions has been hampered by the lack of an animal model. Engrafting NOD/SCID/IL-2-Rg (null) mice with human lymphocytes and thymus, we generated a novel animal model for JCV infection. Mice were inoculated with either a PML isolate, JCV Mad-4, or with JCV CY, found in the kidney and urine of healthy individuals. While mice remained asymptomatic following inoculation, JCV DNA was occasionally detected in both the blood and the urine compartments. Mice generated both humoral and cellular immune responses against JCV. Expressions of immune exhaustion marker, PD-1, on lymphocytes were consistent with response to infection. Using this model we present the first in vivo demonstration of virological and immunological differences between JCV Mad-4 and CY. This model may prove valuable for studying JCV host immune responses.

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Title: Subtitle: Detection of JC Virus-Specific Immune Responses in a Novel Humanized Mouse Model
Creators: Chen Sabrina Tan - Beth Israel Deaconess Medical Center
Thomas A. Broge - Beth Israel Deaconess Medical Center
Edward Seung - Massachusetts General Hospital
Vlad Vrbanac - Massachusetts General Hospital
Raphael Viscidi - Johns Hopkins Bayview Medical Center
Jennifer Gordon - Temple University
Andrew M. Tager - Massachusetts General Hospital
Igor J. Koralnik - Beth Israel Deaconess Medical Center
Resource Type: Journal article
Publication Details: PloS one, Vol.8(6), pp.e64313-e64313
DOI: 10.1371/journal.pone.0064313
PMID: 23700470
PMCID: PMC3658964
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library Science
Number of pages: 9
Grant note: T32AI007061 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01 NS 047029; NS 074995; NS R56 041198; K24 NS 060950 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Harvard University Center for AIDS Research (CFAR) P30 AI60354; K08 NS 064215-01 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01NS074995 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
Language: English
Date published: 05/20/2013
Academic Unit: Iowa Neuroscience Institute; Internal Medicine
Record Identifier: 9984366362502771

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