title: Effects of varicella-zoster virus on cell cycle regulatory pathways.
abstract: Varicella-zoster virus (VZV) grows efficiently in quiescent cells in vivo and in culture, and virus infection activates cell cycle and signaling pathways without cell division. VZV ORFs have been identified that determine the tissue tropism for nondividing skin, T cells, and neurons in SCID-Hu mouse models. The normal cell cycle status of human foreskin fibroblasts was characterized and was dysregulated upon infection by VZV. The expression of cyclins A, B1, and D3 was highly elevated but did not correspond with extensive cellular DNA synthesis. Cell cycle arrest may be due to activation of the DNA damage response during VZV DNA replication. Other host regulatory proteins were induced in infected cells, including p27, p53, and ATM kinase. A possible explanation for the increase in cell cycle regulatory proteins is activation of transcription factors during VZV infection. There is evidence that VZV infection activates transcription factors through the mitogen-activated protein kinase pathways extracellular-regulated kinase (ERK) and c-Jun N-terminal (transpose these parts of the compound noun) kinase (JNK), which could selectively increase cyclin levels. Some of these perturbed cell functions are essential for VZV replication, such as cyclin-dependent kinase (CDK) activity, and reveal targets for interventions.
authors.affiliation: Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA. moffatj@upstate.edu
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Moffat
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Greenblatt
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D002644:Chickenpox / Q000473:pathology* / Q000821:virology; D014645:Herpesvirus 3, Human / Q000502:physiology*; D006801:Humans; D051379:Mice; D015398:Signal Transduction; D014779:Virus Replication
chemical_list: D018797:Cell Cycle Proteins