title: Bovine herpesvirus 1 productive infection and immediate early transcription unit 1 promoter are stimulated by the synthetic corticosteroid dexamethasone.
abstract: The primary site for life-long latency of bovine herpesvirus 1 (BHV-1) is sensory neurons. The synthetic corticosteroid dexamethasone consistently induces reactivation from latency; however the mechanism by which corticosteroids mediate reactivation is unclear. In this study, we demonstrate for the first time that dexamethasone stimulates productive infection, in part, because the BHV-1 genome contains more than 100 potential glucocorticoid receptor (GR) response elements (GREs). Immediate early transcription unit 1 (IEtu1) promoter activity, but not IEtu2 or VP16 promoter activity, was stimulated by dexamethasone. Two near perfect consensus GREs located within the IEtu1 promoter were necessary for dexamethasone-mediated stimulation. Electrophoretic mobility shift assays and chromatin immunoprecipitation studies demonstrated that the GR interacts with IEtu1 promoter sequences containing the GREs. Although we hypothesize that DEX-mediated stimulation of IEtu1 promoter activity is important during productive infection and perhaps reactivation from latency, stress likely has pleiotropic effects on virus-infected cells.
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Morisson Life Science Center, RM234, Lincoln, NE 68583-09065, USA.
authors.forename: Insun
authors.initials: I
authors.lastname: Kook
authors.affiliation: Mississippi State University, Department of Biochemistry and Molecular Biology, Entomology and Plant Pathology, 408 Dorman Hall-Mailstop 9655, 32 Creelman St., Starkville, MS 39762, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Henley
authors.affiliation: Mississippi State University, Department of Biochemistry and Molecular Biology, Entomology and Plant Pathology, 408 Dorman Hall-Mailstop 9655, 32 Creelman St., Starkville, MS 39762, USA.
authors.forename: Florencia
authors.initials: F
authors.lastname: Meyer
authors.affiliation: Mississippi State University, Department of Biochemistry and Molecular Biology, Entomology and Plant Pathology, 408 Dorman Hall-Mailstop 9655, 32 Creelman St., Starkville, MS 39762, USA.
authors.forename: Federico G
authors.initials: FG
authors.lastname: Hoffmann
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Morisson Life Science Center, RM234, Lincoln, NE 68583-09065, USA. Electronic address: clint.jones10@okstate.edu.
authors.forename: Clinton
authors.initials: C
authors.lastname: Jones
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D003907:Dexamethasone / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D007242:Herpesvirus 1, Bovine / Q000187:drug effects* / Q000502:physiology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D020218:Response Elements; D014158:Transcription, Genetic / Q000187:drug effects*; D014775:Virus Activation / Q000187:drug effects*
chemical_list: D000305:Adrenal Cortex Hormones; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone
keywords: BHV-1; Glucocorticoid receptor; Glucocorticoid response element; Immediate early transcription unit 1; Stress-induced viral replication