The virus-induced factor VIF differentially recognizes the virus-responsive modules of the mouse IFNA4 gene promoter

J Interferon Cytokine Res. 2002 Jan;22(1):77-86. doi: 10.1089/107999002753452683.


Maximal activation of murine infection-A4 (IFNA4) gene transcription following viral infection requires the presence of four cooperating DNA sequences (denoted A to D), which make up the virus responsive element VRE-A4. The B, C, and D modules, when tandemized, form binding sites for the virus-induced factor (VIF), a multiprotein complex that is detected early after viral infection in the nuclei of mouse L929 cells. We now demonstrate that IFN regulatory factor-3 (IRF-3) is a component of VIF and that VIF is different from the previously identified virus-activated complexes containing IRF-3 and coactivators of transcription, such as CREB binding protein (CBP) or p300. We also show that the C module is critical for both IRF-3-mediated and virus-induced transcription of the murine IFNA4 gene. Consistently, DNase I footprinting experiments and EMSA performed with increasing amounts of recombinant GST-IRF-3(DBD) fusion proteins demonstrate that cooperativity between the modules facilitate the binding of IRF-3 and recruitment of transcription coactivators on the IFNA4 promoter. These results indicate that VIF differentially recognizes the virus-responsive modules of VRE-A4 and further actualize our previous model concerning the differential expression of murine IFNA genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • CREB-Binding Protein
  • Cell Line
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • E1A-Associated p300 Protein
  • Humans
  • Interferon Regulatory Factor-3
  • Interferon-alpha / genetics*
  • Interferon-alpha / metabolism
  • Macromolecular Substances
  • Mice
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Newcastle disease virus / physiology*
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic*
  • Recombinant Fusion Proteins / metabolism
  • Response Elements*
  • Trans-Activators / metabolism
  • Transcription Factors / analysis
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcriptional Activation


  • DNA-Binding Proteins
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Interferon-alpha
  • Irf3 protein, mouse
  • Macromolecular Substances
  • Multiprotein Complexes
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • CREB-Binding Protein
  • CREBBP protein, human
  • Crebbp protein, mouse
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse