Induction of the early growth response 1 gene by Epstein-Barr virus lytic transactivator Zta

J Virol. 2006 Aug;80(15):7748-55. doi: 10.1128/JVI.02608-05.

Abstract

Early growth response 1 (Egr-1) is a cellular transcription factor involved in diverse biologic functions. Egr-1 has been associated with Epstein-Barr virus (EBV) infection, but it is still unknown whether any EBV protein regulates Egr-1 expression. In this study, we first showed that EBV reactivation is involved in upregulation of Egr-1 and that Egr-1 can be induced by Zta, an EBV lytic transactivator. Zta not only binds to the Egr-1 promoter but also activates the ERK signaling pathway to trigger binding of Elk-1 to the Egr-1 promoter. In addition, knockdown of Egr-1 significantly reduces the spontaneous expression of Zta and Rta in EBV-infected 293 cells, suggesting that a positive-feedback network involving Egr-1 is required for EBV reactivation. This study also implies that Zta has the potential to affect expression of certain genes through Egr-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line
  • DNA-Binding Proteins / physiology*
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / physiology*
  • Epstein-Barr Virus Infections / genetics
  • Epstein-Barr Virus Infections / virology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Viral*
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Immediate-Early Proteins / physiology
  • Kidney / metabolism
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Protein Binding
  • Signal Transduction
  • Trans-Activators / physiology*
  • Transcription, Genetic
  • Transcriptional Activation
  • Viral Proteins / physiology*
  • ets-Domain Protein Elk-1 / genetics
  • ets-Domain Protein Elk-1 / metabolism

Substances

  • BRLF1 protein, Human herpesvirus 4
  • BZLF1 protein, Herpesvirus 4, Human
  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Immediate-Early Proteins
  • Trans-Activators
  • Viral Proteins
  • ets-Domain Protein Elk-1
  • Extracellular Signal-Regulated MAP Kinases