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: Aspen Workman, James Eudy, Lynette Smith, Leticia Frizzo da Silva, Devis Sinani, Halie Bricker, Emily Cook, Alan Doster, Clinton Jones
• Journal: Journal of virology (J Virol) Vol. 86 Issue 5 Pg. 2459-73 (Mar 2012) ISSN: 1098-5514 [Electronic] United States
• PMID: 22190728 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Transcription Factors
• Dexamethasone

Topics

• Animals
• Cattle
• Cattle Diseases (genetics, metabolism, virology)
• Cell Line
• Dexamethasone (pharmacology)
• Gene Expression Regulation, Viral (drug effects)
• Herpesviridae Infections (genetics, metabolism, veterinary, virology)
• Herpesvirus 1, Bovine (drug effects, genetics, physiology)
• Mice
• Promoter Regions, Genetic (drug effects)
• Rabbits
• Transcription Factors (genetics, metabolism)
• Trigeminal Ganglion (metabolism, virology)
• Up-Regulation
• Virus Activation (drug effects)
• Virus Latency (drug effects)