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

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish (US)
Article numbere64313
JournalPloS one
Volume8
Issue number5
DOIs
StatePublished - May 20 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Tan, C. S., Broge, T. A., Seung, E., Vrbanac, V., Viscidi, R., Gordon, J., Tager, A. M., & Koralnik, I. J. (2013). Detection of JC Virus-Specific Immune Responses in a Novel Humanized Mouse Model. PloS one, 8(5), [e64313]. https://doi.org/10.1371/journal.pone.0064313