title: Cellular transcription factors induced in trigeminal ganglia during dexamethasone-induced reactivation from latency stimulate bovine herpesvirus 1 productive infection and certain viral promoters.
abstract: Bovine herpesvirus 1 (BHV-1), an alphaherpesvirinae subfamily member, establishes latency in sensory neurons. Elevated corticosteroid levels, due to stress, reproducibly triggers reactivation from latency in the field. A single intravenous injection of the synthetic corticosteroid dexamethasone (DEX) to latently infected calves consistently induces reactivation from latency. Lytic cycle viral gene expression is detected in sensory neurons within 6 h after DEX treatment of latently infected calves. These observations suggested that DEX stimulated expression of cellular genes leads to lytic cycle viral gene expression and productive infection. In this study, a commercially available assay-Bovine Gene Chip-was used to compare cellular gene expression in the trigeminal ganglia (TG) of calves latently infected with BHV-1 versus DEX-treated animals. Relative to TG prepared from latently infected calves, 11 cellular genes were induced more than 10-fold 3 h after DEX treatment. Pentraxin three, a regulator of innate immunity and neurodegeneration, was stimulated 35- to 63-fold after 3 or 6 h of DEX treatment. Two transcription factors, promyelocytic leukemia zinc finger (PLZF) and Slug were induced more than 15-fold 3 h after DEX treatment. PLZF or Slug stimulated productive infection 20- or 5-fold, respectively, and Slug stimulated the late glycoprotein C promoter more than 10-fold. Additional DEX-induced transcription factors also stimulated productive infection and certain viral promoters. These studies suggest that DEX-inducible cellular transcription factors and/or signaling pathways stimulate lytic cycle viral gene expression, which subsequently leads to successful reactivation from latency in a small subset of latently infected neurons.
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, Lincoln, Nebraska, USA.
authors.forename: Aspen
authors.initials: A
authors.lastname: Workman
authors.forename: James
authors.initials: J
authors.lastname: Eudy
authors.forename: Lynette
authors.initials: L
authors.lastname: Smith
authors.forename: Leticia Frizzo
authors.initials: LF
authors.lastname: da Silva
authors.forename: Devis
authors.initials: D
authors.lastname: Sinani
authors.forename: Halie
authors.initials: H
authors.lastname: Bricker
authors.forename: Emily
authors.initials: E
authors.lastname: Cook
authors.forename: Alan
authors.initials: A
authors.lastname: Doster
authors.forename: Clinton
authors.initials: C
authors.lastname: Jones
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D007242:Herpesvirus 1, Bovine / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011817:Rabbits; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000378:metabolism* / Q000821:virology; D015854:Up-Regulation; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency / Q000187:drug effects
chemical_list: D014157:Transcription Factors; D003907:Dexamethasone