Transcriptional activation of JC virus early promoter by phorbol ester and interleukin-1beta: critical role of nuclear factor-1.

Abstract

JC virus causes the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML) under immunosuppressive states such as AIDS. During the pathogenesis of AIDS, HIV-infected microglia secrete cytokines including interleukin-1 and tumor necrosis factor-alpha (TNF-alpha), which affect neuronal cells resulting in dysfunction of the CNS. We hypothesized that extracellular stimuli released from HIV-infected microglia may reactivate JC virus by affecting neighboring oligodendrocytes. In the present study, we found that phorbol myristate acetate (PMA) and interleukin-1beta (IL-1beta) dramatically increased JC virus transcription in glial cells. Site-directed mutagenesis and gel shift analyses revealed that PMA and IL-1beta strongly induced nuclear factor-1 (NF-1) binding to the JC virus enhancer region, increasing transcriptional activity of the viral early promoter. Additionally, we demonstrated that protein kinase C (PKC) pathways were involved in the PMA/IL-1beta-mediated up-regulation of the JC virus early promoter. These findings may represent one of the possible mechanisms for higher incidence of PML among AIDS patients.

• Authors: So-Young Kim, Eung-Chil Choi, Yeong Woo Jo, John W Henson, Hee-Sun Kim
• Journal: Virology (Virology) Vol. 327 Issue 1 Pg. 60-9 (Sep 15 2004) ISSN: 0042-6822 [Print] United States
• PMID: 15327898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCAAT-Enhancer-Binding Proteins
• Interleukin-1
• NFI Transcription Factors
• Phorbol Esters
• Transcription Factors

Topics

• Base Sequence
• Binding Sites
• CCAAT-Enhancer-Binding Proteins (chemistry, metabolism)
• Cell Line, Tumor
• Humans
• Interleukin-1 (pharmacology)
• JC Virus (genetics, metabolism)
• Molecular Sequence Data
• Mutagenesis, Site-Directed
• NFI Transcription Factors
• Phorbol Esters (pharmacology)
• Promoter Regions, Genetic (genetics, physiology)
• Transcription Factors (chemistry, metabolism)
• Transcriptional Activation (drug effects)