title: Varicella-zoster virus (VZV) mediates a delayed host shutoff independent of open reading frame (ORF) 17 expression.
abstract: Varicella-zoster virus (VZV) open reading frame 17 (ORF 17) is the gene corresponding to Herpes simplex-virus (HSV) UL41. The UL41 gene encodes the virion host shutoff factor (vhs), a RNase that has been the object of detailed studies. In contrast to HSV, knowledge about VZV mediated shutoff effects and the role of ORF 17 is poor. We investigated the ORF 17 expression in infected cells and analyzed shutoff effects. ORF 17 expression could not be proven in infected human fibroblast cell lines and melanoma (MeWo) cells. Only after induction by Phorbol 12-myristate 13-acetate an ORF 17 expression became detectable in MeWo cells. Nevertheless, using stable expressed GAPDH mRNA as a marker for mRNA degradation, a VZV mediated shutoff, independent of ORF 17 expression, became measurable. Transfection experiments demonstrated that transient ORF 17 expression did not decrease the cellular GAPDH mRNA level. We examined whether the VZV shutoff factor is a tegument protein causing an early shutoff or whether it needs to be expressed (delayed shutoff). The GAPDH mRNA level in Actinomycin D pretreated and infected MeWo cells did not decrease even faster than the theoretical decay rate based on a half-life of 24 h. These findings lead to the conclusion that the VZV shutoff factor is not a mature protein localized in the virion and that VZV causes a delayed virion host shutoff effect.
authors.affiliation: Institute of Microbiology and Virology, University of Witten/Herdecke, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.forename: Markus
authors.initials: M
authors.lastname: Rahaus
authors.forename: Manfred H
authors.initials: MH
authors.lastname: Wolff
mesh_terms: D015152:Blotting, Northern; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D005814:Genes, Viral; D014645:Herpesvirus 3, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016366:Open Reading Frames / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000096:biosynthesis; D012260:Ribonucleases / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000096:biosynthesis / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; D012260:Ribonucleases; D013755:Tetradecanoylphorbol Acetate