Murine cytomegalovirus infection induces cellular folylpolyglutamate synthetase activity in quiescent cells

Cytomegalovirus (CMV) infection stimulates the expression of cellular enzym es involved in the biosynthesis of DNA precursors. Among them, dihydrofolat e reductase (DHFR) and thymidylate synthase (TS) require folate as coenzyme s. In growing cells, folates are readily converted to polyglutamated forms by the cellular enzyme folylpolyglutamate synthetase (FPGS). Polyglutamated folates are selectively retained within the cell and have an increased aff inity for DHFR and TS. Here we report that murine CMV (MCMV) increases the levels of the FPGS mRNAs as well as the enzymatically active FPGS protein t hrough a mechanism that requires viral gene expression. FPGS induction by M CMV would provide the necessary supply of polyglutamated folates to the cel lular enzymes involved in the biosynthesis of deoxyribonucleotides, enablin g viral DNA replication to take place in quiescent cells. Copyright (C) 200 1 S. Karger AG, Basel.