INHIBITION OF CELLULAR CDK2 ACTIVITY BLOCKS HUMAN CYTOMEGALOVIRUS REPLICATION

Human cytomegalovirus is a herpesvirus that induces numerous cellular processes upon infection. Among these are activation of cyclin-depende nt kinase 2, which regulates cell cycle progression in G1 and S phase. We report here that inhibition of cellular Cdk2 activity blocks HCMV replication. Inhibition of Cdk2 activity by roscovitine inhibits HCMV DNA synthesis, production of infectious progeny, and late antigen expr ession in infected cells in a dose-dependent manner. HCMV replication is also inhibited by the expression of a Cdk2 dominant negative mutant , whereas expression of wild-type Cdk2 has no effect on viral replicat ion. These data indicate that activation of cellular Cdk2 is necessary for HCMV replication. (C) 1997 Academic Press.