Tumour necrosis factor alpha stimulates the activity of the human cytomegalovirus major immediate early enhancer/promoter in immature monocytic cells.
Both tumour necrosis factor alpha (TNF-alpha) and phorbol 12-myristate 13-acetate (PMA) stimulated human cytomegalovirus (HCMV) major immediate early (IE) enhancer/promoter activity in the HL-60 granulocyte/monocyte progenitor cell line when added to transfected cells. In U-937 monocytic cells, by contrast, TNF-alpha had no stimulatory effect and the addition of PMA produced only marginal stimulation. In the mature THP-1 monocytic cell line and in differentiated HL-60 cells, addition of TNF-alpha caused inhibition of the IE enhancer/promoter activity. The stimulating effect of PMA, as observed in the other cell lines, however, remained. Thus the effect of TNF-alpha on the major IE enhancer/promoter activity is determined by the degree of differentiation of the infected cells. Unlike TNF-alpha and PMA, the interleukins IL-1, IL-3, IL-6 as well as the cytokine GM-CSF were found to have no detectable influence on the activity of the IE enhancer/promoter activity which, likewise, was not affected by the presence of the modulator sequence. Since premonocytic cells are suggested to be sites of HCMV latency, the stimulation by TNF-alpha could be of potential pathophysiological significance.
Stein
J
J
Institute of Virology, Humboldt University Medical School (Charité), Berlin, Germany.
Volk
H D
HD
Liebenthal
C
C
Krüger
D H
DH
Prösch
S
S
D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D009000:Monocytes / Q000382:microbiology*; D011401:Promoter Regions, Genetic; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D017874:Immediate-Early Proteins; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate