Human Cytomegalovirus Stimulates Thymidylate Synthase in Human Embryonic Lung Cells: A Possible Target for Anti-HCMV Therapy?

Abstract

We have demonstrated that thymidylate synthase (TS) activity is enhanced 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 parallel the progression of the viral cytopathic effect over a 5-days period, (ii) to be independent of viral DNA synthesis and to result from an early event in the viral replicative cycle. Several compounds known 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 compounds remains however to be determined.