The effects of human cytomegalovirus challenge on the proliferation and inhibitor production of myeloid cells U-937 and THP-1

This project examines the effects of HCMV infection on cell proliferation, differentiation, as well as on the growth factor production of myeloid cells during the myelopoiesis. The major focus is on the effects of the challenge of HCMV AD 169 strain on the proliferation and inhibitor production of U-937 and THP-1 cells in the presence or absence of retinoic acid. In the present study, promonocytic U-937 and THP-1 cells were treated with 500 nM retinoic acid. These two cell lines are known as leukemia cells which are blocked at a relatively late stage along the myelopoiesis. Treatement of both cell lines with retinoic acid for a period of 6 days could markedly inhibit the cell proliferation, as measured by the counts of viable cell number and the level of [^H] TdR incorporation. Concomitant with the retinoic acid-associated suppression of cell proliferation was the appearance of indented, kidney shaped nuclei and a time-dependent increase in the percentage of cells reducing nitroblue tetrazolium , which are characteristic for differentiated monocytes. Promonocytic U-937 and THP-1 cells spontaneously produced factors which inhibited the proliferation of murine thymocytes primed with phytohaemagglutinin and rIL-2. However this suppression became less effective when both cell lines were differentiating in the presence of retinoic acid. HCMV challenge could suppress the proliferation of promonocytic U-937 and THP-1 cells. This suppression effect appeared to be independent of the infectivity of the virus as both infectious and UV-inactivated HCMV suppressed the cell proliferation to a similar extent. Challenge of U-937 and THP-1 cells with HCMV could disturb their inhibitor production and the extent of the disturbation was very likely dependent upon the intracellular status of both cell lines in the presence of RA. In conclusion, this project expands our understanding of the highly complex interaction which occurs between cells of U-937 and THP-1 and HCMV during the process of cell proliferation and differentiation.