Human cytomegalovirus stimulates cellular dihydrofolate reductase activityin quiescent cells

Human cytomegalovirus (HCMV) productively infects quiescent fibroblasts in which the levels of deoxynucleotide triphosphates (dNTPs) and cell function s involved in DNA metabolism are very low. Since sufficient dNTPs levels ar e essential for human HCMV replication, host cell enzymes involved in the b iosynthesis of dNTPs might be expected to be stimulated by viral infection in quiescent cells. We report that HCMV infection of quiescent fibroblasts stimulates the activity of cellular dihydrofolate reductase (DHFR), a key e nzyme in DNA precursor synthesis. We also demonstrate that suppression of D HFR activity by the specific inhibitor methotrexate prevents HCMV replicati on and DNA synthesis. These observations indicate that induction of DHFR ac tivity by HCMV is required for efficient viral replication in quiescent fib roblasts.