TUMOR-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 immedi ate early (IE) enhancer/promoter activity in the HL-60 granulocyte/mon ocyte progenitor cell line when added to transfected cells. In U-937 m onocytic cells, by contrast, TNF-alpha had no stimulatory effect and t he addition of PMA produced only marginal stimulation. In the mature T HP-1 monocytic cell line and in differentiated HL-60 cells, addition o f TNF-alpha caused inhibition of the IE enhancer/promoter activity. Th e stimulating effect of PMA, as observed in the other cell lines, howe ver, remained. Thus the effect of TNF-alpha on the major IE enhancer/p romoter 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, t he stimulation by TNF-alpha could be of potential pathophysiological s ignificance.