Stimulation of the human cytomegalovirus IE enhancer/promoter in HL-60 cells by TNFalpha is mediated via induction of NF-kappaB
- PMID: 11831701
- DOI: 10.1006/viro.1995.1143
Stimulation of the human cytomegalovirus IE enhancer/promoter in HL-60 cells by TNFalpha is mediated via induction of NF-kappaB
Abstract
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.
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