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-dependent 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 expression 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 replication. These data indicate that activation of cellular Cdk2 is necessary for HCMV replication.
Bresnahan
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Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77550, USA.
Boldogh
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I
Chi
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Thompson
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EA
Albrecht
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T
D000956:Antigens, Viral / Q000096:biosynthesis; D042846:CDC2-CDC28 Kinases; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000378:metabolism; D003587:Cytomegalovirus / Q000254:growth & development*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011687:Purines / Q000494:pharmacology; D000077546:Roscovitine; D014779:Virus Replication / Q000187:drug effects*
D000956:Antigens, Viral; D016213:Cyclins; D004791:Enzyme Inhibitors; D011687:Purines; D000077546:Roscovitine; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases