Cooperative roles of NF-?B and NFAT4 in polyomavirus JC regulation at the KB control element.

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Cooperative roles of NF-?B and NFAT4 in polyomavirus JC regulation at the KB control element.

Virology. 2012 Oct 10;432(1):146-54

Authors: Wollebo HS, Melis S, Khalili K, Safak M, White MK

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-?B and C/EBP? 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-? on JCV gene expression. Other studies have implicated NFAT4 in JCV regulation. We now report that NFAT4 and NF-?B 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/EBP? 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.

PMID: 22749879 [PubMed - in process]

NF-kB signaling pathway NF-kB pathway NF-kB signaling