Document Detail


Transcriptional activation of JC virus early promoter by phorbol ester and interleukin-1beta: critical role of nuclear factor-1.
MedLine Citation:
PMID:  15327898     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Virology     Volume:  327     ISSN:  0042-6822     ISO Abbreviation:  Virology     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-25     Completed Date:  2004-09-28     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  60-9     Citation Subset:  IM    
Affiliation:
Department of Neuroscience, Ewha Institute of Neuroscience and Medical Research Center, Ewha Womans University School of Medicine, Seoul, South Korea.
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MeSH Terms
Descriptor/Qualifier:
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*
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Proteins; 0/Interleukin-1; 0/NFI Transcription Factors; 0/Phorbol Esters; 0/Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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