The cellular transcription factor, CCAAT enhancer-binding protein alpha (C/EBP-α), has the potential to activate the bovine herpesvirus 1 immediate-early transcription unit 1 promoter

Florencia Meyer, Clinton Jones

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Following acute infection, bovine herpesvirus-1 (BHV-1) establishes a lifelong latent infection in sensory neurons of trigeminal ganglia. BHV-1 periodically reactivates from latency and is shed as infectious virus. The latency-related (LR) gene is abundantly expressed in trigeminal ganglia of infected calves, and proteins encoded by the LR gene are necessary for reactivation from latency. We previously demonstrated that a novel LR protein interacts with a host transcription factor, CCAAT enhancer-binding protein alpha (C/EBPα). C/EBPα increases plaque-forming efficiency when cotransfected with BHV-1 DNA and its expression is induced in neurons during reactivation from latency (Meyer et al, 2007, J Virol 81: 59-67). The ability of C/EBPα to bind DNA is necessary for stimulating productive infection, suggesting C/EBPα stimulates viral transcription. We tested whether C/EBPα could trans-activate the BHV-1 immediate early transcription unit 1 (IEtu1) promoter because the IEtu1 promoter activates expression of two viral genes (bICP0 and bICP4) that stimulate producitve infection. In the current study, We demonstrate that C/EBPα and the BHV-1 trans-inducing factor (bTIF) synergistically trans-activate IEtu1 promoter activity. However, bICP0 and C/EBPα did not synergistically trans-activate IEtu1 promoter activity. Deletion of IEtu1 promoter sequences demonstrated that C/EBPα by itself could trans-activate a truncated IEtu1 promoter, suggesting sequences in the distal region of the IEtu1 promoter negatively regulate C/EBPα activtiy. These studies suggest that C/EBPα stimulates productive infection and reactivation from latency, in part, by cooperating with bTIF to activate IEtu1 promoter activity.

Original languageEnglish (US)
Pages (from-to)123-130
Number of pages8
JournalJournal of neurovirology
Volume15
Issue number2
DOIs
StatePublished - 2009

Keywords

  • Bovine herpesvirus1
  • C/EBP-alpha
  • Gene expression

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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