title: The varicella-zoster virus-mediated delayed host shutoff: open reading frame 17 has no major function, whereas immediate-early 63 protein represses heterologous gene expression.
abstract: We reported that varicella-zoster virus (VZV) causes a delayed host shutoff during its replicative cycle. VZV open reading frame 17 (ORF17) is the homologue of the herpes simplex virus (HSV) UL41 gene encoding the virion host shutoff (vhs) protein which is responsible for the shutoff effect observed in HSV-infected cells. In the present study, we demonstrated that ORF17 is expressed as a late protein during the VZV replicative cycle in different infected permissive cell lines which showed a delayed shutoff of cellular RNA. A cell line with stable expression of VZV ORF17 was infected with VZV. In these cells, VZV replication and delayed host shutoff remained unchanged when compared to normal infected cells. ORF17 was not capable of repressing the expression of the beta-gal reporter gene under the control of the human cytomegalovirus immediate-early gene promoter or to inhibit the expression of a CAT reporter gene under the control of the human GAPDH promoter, indicating that ORF17 has no major function in the VZV-mediated delayed host shutoff. To determine whether other viral factors are involved in the host shutoff, a series of cotransfection assays was performed. We found that the immediate-early 63 protein (IE63) was able to downregulate the expression of reporter genes under the control of the two heterologous promoters, indicating that this viral factor can be involved in the VZV-mediated delayed host shutoff. Other factors can be also implicated to modulate the repressing action of IE63 to achieve a precise balance between the viral and cellular gene expression.
authors.affiliation: Institute of Microbiology and Virology, Private University of Witten/Herdecke, Stockumer Street 10, D-58448, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Desloges
authors.forename: Markus
authors.initials: M
authors.lastname: Rahaus
authors.forename: Manfred H
authors.initials: MH
authors.lastname: Wolff
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis; D006224:Cricetinae; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005814:Genes, Viral; D014645:Herpesvirus 3, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D014759:Viral Envelope Proteins / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000502:physiology*; D014779:Virus Replication; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D017874:Immediate-Early Proteins; C468297:ORF17 protein, varicella-zoster virus; D012333:RNA, Messenger; D012367:RNA, Viral; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C074551:immediate early protein 63, Human herpesvirus 3; D012313:RNA; D015500:Chloramphenicol O-Acetyltransferase; D001616:beta-Galactosidase