Veterinary and Biomedical Sciences, Department of

 

Date of this Version

2013

Citation

JVI Accepts, published online ahead of print on 7 August 2013.

Published in J. Virol. (2013) 32 pages. DOI:10.1128/JVI.01737-13

Comments

Copyright © 2013, American Society for Microbiology. All Rights Reserved.

Abstract

Bovine herpesvirus 1 (BHV-1) establishes a life-long latent infection in sensory neurons following acute infection. Increased corticosteroid levels, due to stress, increases the incidence of reactivation from latency. Within minutes, corticosteroids activate the glucocorticoid receptor and transcription of promoters containing a glucocorticoid receptor element. A single intravenous injection of the synthetic corticosteroid dexamethasone consistently induces reactivation from latency in calves. Lytic cycle viral gene expression is detected within 6 hours after dexamethasone treatment of calves latently infected with BHV-1. Cellular transcription factors are induced by dexamethasone in trigeminal ganglionic neurons within 1.5 hours after dexamethasone treatment suggesting they promote viral gene expression during the early phases of reactivation from latency, which we operationally defined as the escape from latency. In this study, immunohistochemistry was utilized to examine viral protein expression during the escape from latency. Within 1.5 hours after dexamethasone treatment, bICP0 and a late protein (VP16) were consistently detected in a subset of trigeminal ganglionic neurons. Most neurons expressing bICP0 also expressed VP16. Additional studies revealed that neurons expressing the glucocorticoid receptor also expressed bICP0 or VP16 at 1.5 hours after dexamethasone treatment. Two other late proteins, glycoprotein C and D, were not detected until 6 hours after dexamethasone treatment and were detected in only a few neurons. These studies provide evidence that VP16 and the promiscuous viral trans-activator (bICP0) are expressed during the escape from latency suggesting they promote the production of infectious virus in a small subset of latently infected neurons.

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