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Transcriptional activation of JC virus early promoter by phorbol ester and interleukin-1β: critical role of nuclear factor-1
- Source :
- Virology. (1):60-69
- Publisher :
- Elsevier Inc.
-
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.
- Subjects :
- Transcriptional Activation
Molecular Sequence Data
JC virus
Biology
medicine.disease_cause
Pathogenesis
NF-1
Progressive multifocal leukoencephalopathy
Cell Line, Tumor
Virology
Phorbol Esters
medicine
Demyelinating disease
Humans
Promoter Regions, Genetic
Enhancer
PKC pathway
Protein kinase C
PMA
Binding Sites
Base Sequence
Microglia
medicine.disease
Molecular biology
AIDS
NFI Transcription Factors
medicine.anatomical_structure
IL-1β
CCAAT-Enhancer-Binding Proteins
Mutagenesis, Site-Directed
Tumor necrosis factor alpha
Interleukin-1
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 00426822
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Virology
- Accession number :
- edsair.doi.dedup.....ef1b941387a01d0c666e5e1e4761b047
- Full Text :
- https://doi.org/10.1016/j.virol.2004.06.021