HUMAN CYTOMEGALOVIRUS STIMULATES THYMIDYLATE SYNTHASE IN HUMAN EMBRYONIC LUNG-CELLS - A POSSIBLE TARGET FOR ANTI-HCMV THERAPY

We have demonstrated that thymidylate synthase (TS) activity is enhanc ed by more than 10- to 20-fold in HCMV-infected HEL cells as compared to non-infected cells. The increase in TS activity was found (i) to pa rallel the progression of the viral cytopathic effect over a 5-days pe riod, (ii) to be independent of viral DNA synthesis and to result from an early event in the viral replicative cycle. Several compounds know n to be targeted at TS, such as 5-fluoro-dUrd, 5-trifluoromethyl-dUrd, and 5-formyl-dUrd, inhibited TS activity in HCMV-infected cells and, concomitantly, displayed HCMV activity. The exact impact of inhibition of TS activity in the overall anti-HCMV activity of the test compound s remains however to be determined.