Stimulation of bovine herpesvirus-1 productive infection by the adenovirus E1A gene and a cell cycle regulatory gene, E2F-4

J Gen Virol. 2003 Apr;84(Pt 4):929-938. doi: 10.1099/vir.0.18915-0.


Identifying cellular genes that promote bovine herpesvirus-1 (BHV-1) productive infection is important, as BHV-1 is a significant bovine pathogen. Previous studies demonstrated that BHV-1 DNA is not very infectious unless cotransfected with a plasmid expressing bICP0, a viral protein that stimulates expression of all classes of viral promoters. Based on these and other studies, we hypothesize that the ability of bICP0 to interact with and modify the function of cellular proteins stimulates virus transcription. If this prediction is correct, cellular proteins that activate virus transcription could, in part, substitute for bICP0 functions. The adenovirus E1A gene and bICP0 encode proteins that are potent activators of viral gene expression, they do not specifically bind DNA and both proteins interact with chromatin-remodelling enzymes. Because of these functional similarities, E1A was tested initially to see if it could stimulate BHV-1 productive infection. E1A consistently stimulates BHV-1 productive infection, but not as efficiently as bICP0. The ability of E1A to bind Rb family members plays a role in stimulating productive infection, suggesting that E2F family members activate productive infection. E2F-4, but not E2F-1, E2F-2 or E2F-5, activates productive infection with similar efficiency as E1A. Next, E2F family members were examined for their ability to activate the BHV-1 immediate-early (IE) transcription unit 1 (IEtu1) promoter, as it regulates IE expression of bICP0 and bICP4. E2F-1 and E2F-2 strongly activate the IEtu1 promoter, but not a BHV-1 IEtu2 promoter or a herpes simplex virus type 1 ICP0 promoter construct. These studies suggest that E2F family members can stimulate BHV-1 productive infection.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenovirus E1A Proteins / genetics
  • Adenovirus E1A Proteins / physiology*
  • Animals
  • Cell Cycle Proteins / physiology
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F2 Transcription Factor
  • E2F4 Transcription Factor
  • E2F5 Transcription Factor
  • Gene Expression Regulation, Viral*
  • Herpesviridae Infections / virology*
  • Herpesvirus 1, Bovine / genetics*
  • Herpesvirus 1, Bovine / pathogenicity
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism
  • Promoter Regions, Genetic
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Ubiquitin-Protein Ligases
  • Up-Regulation
  • Viral Proteins
  • Virulence


  • Adenovirus E1A Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F2 Transcription Factor
  • E2F4 Transcription Factor
  • E2F5 Transcription Factor
  • Immediate-Early Proteins
  • Trans-Activators
  • Transcription Factors
  • Viral Proteins
  • Ubiquitin-Protein Ligases
  • Vmw110 protein, Human herpesvirus 1
  • bICP0 protein, Bovine herpesvirus 1