Stimulation of the human cytomegalovirus IE enhancer/promoter in HL-60 cells by TNFalpha is mediated via induction of NF-kappaB

Virology. 1995 Apr 1;208(1):197-206. doi: 10.1006/viro.1995.1143.


TNFalpha enhances the basal activity of the major Immediate Early (IE) enhancer/promoter of human cytomegalovirus (HCMV) in the immature premonocytic HL-60 cell line. The stimulatory effect of TNFalpha is mediated by induction of the transcription factor NF-kappaB, which specifically binds to the 18-bp repetitive sequence motif of the enhancer region. Complex formation could be competed by oligonucleotides representing the 18-bp sequence motif or the prototype NF-kappaB sequence of the immunoglobulin kappa gene. In gel mobility shift assays antisera specific to NF-kappaB p50 and p65 subunits were shown to react with the DNA-protein complex. Addition of the antioxidant PDTC blocked TNFalpha-mediated stimulation in a dose dependent manner. Electrophoretic mobility shift assays indicated that PDTC prevents NF-kappaB induction. Furthermore, it is suggested that protein kinases like PK-C are involved in the TNFalpha signal transduction pathway which leads to the activation of NF-kappaB and its binding to the HCMV IE enhancer in HL-60 cells. Our data are consistent with a role of TNFalpha in reactivation of latent HCMV infection in premonocytic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / genetics*
  • Antigens, Viral / metabolism
  • Cytomegalovirus / physiology*
  • Cytomegalovirus Infections / metabolism
  • Cytomegalovirus Infections / virology*
  • Dose-Response Relationship, Drug
  • HL-60 Cells
  • Humans
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / metabolism
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Virus Replication / drug effects
  • Virus Replication / genetics


  • Antigens, Viral
  • Immediate-Early Proteins
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • immediate-early proteins, cytomegalovirus