title: Role for tumor necrosis factor-α in JC virus reactivation and progressive multifocal leukoencephalopathy.
abstract: JCV causes the CNS demyelinating disease progressive multifocal leukoencephalopathy (PML). After primary infection, JCV persists in a latent state, where viral protein expression and replication are not detectable. NF-κB and C/EBPβ regulate the JCV promoter via a control element, κB, suggesting proinflammatory cytokines may reactivate JCV to cause PML, e.g., in HIV-1/AIDS. Since HIV-1 induces cytokines in brain, including TNF-α, we examined a role for TNF-α in JCV regulation. TNF-α stimulated both early and late JCV transcription. Further, the κB element conferred TNF-α response to a heterologous promoter. Immunohistochemistry of HIV+/PML revealed robust labeling for TNF-α and TNFR-1. These data suggest TNF-α stimulation of κB may contribute to JCV reactivation in HIV+/PML.
authors.affiliation: Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Hassen S
authors.initials: HS
authors.lastname: Wollebo
authors.forename: Mahmut
authors.initials: M
authors.lastname: Safak
authors.forename: Luis
authors.initials: L
authors.lastname: Del Valle
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: Martyn K
authors.initials: MK
authors.lastname: White
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology; D002460:Cell Line; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D007577:JC Virus / Q000235:genetics / Q000276:immunology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015533:Transcriptional Activation / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014775:Virus Activation / Q000235:genetics / Q000276:immunology*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha