D. Lembo et al., Overexpression of cellular dihydrofolate reductase abolishes the anticytomegaloviral activity of methotrexate, ARCH VIROL, 144(7), 1999, pp. 1397-1403
Cytomegalovirus (CMV) stimulates numerous cellular pathways upon infection.
One of these pathways involves activation of dihydrofolate reductase (DHFR
), an essential enzyme in the biosynthesis of purines and thymidylate. Here
we report that methotrexate (MTX), an inhibitor of DHFR, suppresses murine
CMV replication at the level of DNA synthesis in quiescent NIH 3T3 cells.
However, MTX has no antiviral activity in NIH 3T3 sublines resistant to MTX
due to DHFR overexpression. These results directly link MTX antiviral acti
vity to DHFR and demonstrate that DHFR plays an essential role for CMV repl
ication in quiescent cells.