title: Distinct responses of the herpes simplex virus and varicella zoster virus immediate early promoters to the cellular transcription factors Brn-3a and Brn-3b.
abstract: The related viruses herpes simplex virus (HSV) and varicella zoster virus (VZV) show distinct but related patterns of latent infection and reactivation in human sensory ganglia. The cellular POU family transcription factors Brn-3a and Brn-3b are expressed in sensory ganglia and bind to the TAATGARAT (R stands for purine) regulatory motifs in the immediate-early gene promoters of these viruses. We show that Brn-3a activates the full length HSV IE1 promoter whereas Brn-3b represses its activity. In contrast both Brn-3a and Brn-3b activate the full length VZV IE promoter. The response of the full length VZV promoter to Brn-3b is not observed with a minimal VZV immediate-early promoter lacking any TAATGARAT elements and cannot be restored by addition of either the upstream TAATGARAT-containing region of the HSV IE promoter or a VZV TAATGARAT-like element to this minimal promoter. The unique effect of Brn-3b on the full length VZV immediate early gene promoter may play a key role in the distinct pattern of latent infection and reactivation observed with this virus in vivo.
authors.affiliation: Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London Medical School, UK.
authors.forename: J
authors.initials: J
authors.lastname: Brownlees
authors.forename: G
authors.initials: G
authors.lastname: Gough
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.forename: P
authors.initials: P
authors.lastname: Watts
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.forename: R
authors.initials: R
authors.lastname: Coffin
authors.forename: D S
authors.initials: DS
authors.lastname: Latchman
mesh_terms: D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017781:Genes, Immediate-Early; D014645:Herpesvirus 3, Human / Q000378:metabolism*; D006801:Humans; D008957:Models, Genetic; D010957:Plasmids; D011401:Promoter Regions, Genetic; D018139:Simplexvirus / Q000378:metabolism*; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C494188:POU4F1 protein, human; C494190:POU4F2 protein, human; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase