Transcriptional activation of JC virus early promoter by phorbol ester and interleukin-1β: Critical role of nuclear factor-1

So Young Kim, Eung Chil Choi, Yeong Woo Jo, John W. Henson, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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-α (TNF-α), 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-1β (IL-1β) dramatically increased JC virus transcription in glial cells. Site-directed mutagenesis and gel shift analyses revealed that PMA and IL-1β 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-1β-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.

Original languageEnglish (US)
Pages (from-to)60-69
Number of pages10
JournalVirology
Volume327
Issue number1
DOIs
StatePublished - Sep 15 2004
Externally publishedYes

Keywords

  • AIDS
  • IL-1β
  • JC virus
  • NF-1
  • PKC pathway
  • PMA
  • Progressive multifocal leukoencephalopathy

ASJC Scopus subject areas

  • Virology

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