title: Viral and cellular kinases are potential antiviral targets and have a central role in varicella zoster virus pathogenesis.
abstract: Herpesviruses utilize viral and cellular kinases for replication, and these mediate essential functions that are important for viral pathogenesis. Elucidating the roles of kinases in herpesvirus infections may highlight virus-host interactions that are possible targets for kinase inhibitors with antiviral activity. Varicella zoster virus (VZV) encodes two kinases that phosphorylate viral proteins involved in regulation, assembly, and virulence. VZV infection also induces the activity of host cell cyclin-dependent kinases (cdk4 and cdk2) in nondividing cells, causing a disregulation of the cell cycle. Roscovitine and Purvalanol, kinase inhibitors that target cdks, prevent VZV replication at concentrations with few cytotoxic effects. Cdk inhibitors therefore have potential as antivirals that may extend to a broad range of viruses and have the added advantage that resistance does not arise easily.
authors.affiliation: Department of Microbiology and Immunology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. moffatj@upstate.edu
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Moffat
authors.forename: Michelle A
authors.initials: MA
authors.lastname: McMichael
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Leisenfelder
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Taylor
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D014645:Herpesvirus 3, Human / Q000201:enzymology* / Q000472:pathogenicity; D006801:Humans; D011687:Purines / Q000737:chemistry / Q000494:pharmacology; D000077546:Roscovitine; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011687:Purines; D000077546:Roscovitine; D018844:Cyclin-Dependent Kinases