Role for tumor necrosis factor-alpha in JC virus reactivation and progressive multifocal leukoencephalopathy

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-kappa B and C/EBP beta regulate the JCV promoter via a control element, kappa B, suggesting proinflammatory cytokines may reactivate JCV to cause PML, e.g., in HIV-1/AIDS. Since HIV-1 induces cytokines in brain, including TNF-alpha, we examined a role for TNF-alpha in JCV regulation. TNF-alpha stimulated both early and late JCV transcription. Further, the kappa B element conferred TNF-alpha response to a heterologous promoter. Immunohistochemistry of HIV+/PML revealed robust labeling for TNF-alpha and TNFR-1. These data suggest TNF-alpha stimulation of kappa B may contribute to JCV reactivation in HIV+/PML. (C) 2010 Elsevier B.V. All rights reserved.