title: Cooperative roles of NF-κB and NFAT4 in polyomavirus JC regulation at the KB control element.
abstract: The human polyomavirus JC (JCV) is the causative agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy (PML). Infection by JCV is extremely common and after primary infection, JCV persists in a latent state. However, PML is a very rare disease suggesting that the virus is tightly regulated. Previously, we showed that NF-κB and C/EBPβ regulate the JCV early and late promoters via a DNA control element, KB, which also mediates the stimulatory effects of proinflammatory cytokines such as TNF-α on JCV gene expression. Other studies have implicated NFAT4 in JCV regulation. We now report that NFAT4 and NF-κB interact at the KB element to co-operatively activate both JCV early and late transcription and viral DNA replication. This interplay is inhibited by C/EBPβ and by agents that block the calcineurin/NFAT signaling pathway. The importance of these events in the regulation of JCV latency and reactivation is discussed.
authors: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors: Hassen S
authors: HS
authors: Wollebo
authors: Sonia
authors: S
authors: Melis
authors: Kamel
authors: K
authors: Khalili
authors: Mahmut
authors: M
authors: Safak
authors: Martyn K
authors: MK
authors: White
mesh_terms: D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D007577:JC Virus / Q000235:genetics* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014775:Virus Activation; D014779:Virus Replication
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494008:NFATC3 protein, human