title: Detection of JC virus-specific immune responses in a novel humanized mouse model.
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.
authors.affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. ctan@bidmc.harvard.edu
authors.forename: Chen Sabrina
authors.initials: CS
authors.lastname: Tan
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Broge
authors.forename: Edward
authors.initials: E
authors.lastname: Seung
authors.forename: Vlad
authors.initials: V
authors.lastname: Vrbanac
authors.forename: Raphael
authors.initials: R
authors.lastname: Viscidi
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gordon
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tager
authors.forename: Igor J
authors.initials: IJ
authors.lastname: Koralnik
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000943:Antigens, Differentiation / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology; D019556:COS Cells; D036022:Capsid Proteins / Q000276:immunology; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000097:blood / Q000652:urine; D004195:Disease Models, Animal; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007577:JC Virus / Q000235:genetics / Q000276:immunology*; D007668:Kidney / Q000821:virology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D061026:Programmed Cell Death 1 Receptor
chemical_list: D000914:Antibodies, Viral; D000943:Antigens, Differentiation; D000956:Antigens, Viral; D036022:Capsid Proteins; D004279:DNA, Viral; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor