Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300

EMBO J. 1998 Feb 16;17(4):1087-95. doi: 10.1093/emboj/17.4.1087.


It has been hypothesized that certain viral infections directly activate a transcription factor(s) which is responsible for the activation of genes encoding type I interferons (IFNs) and interferon-stimulated genes (ISGs) via interferon regulatory factor (IRF) motifs present in their respective promoters. These events trigger the activation of defense machinery against viruses. Here we demonstrate that IRF-3 transmits a virus-induced signal from the cytoplasm to the nucleus. In unstimulated cells, IRF-3 is present in its inactive form, restricted to the cytoplasm due to a continuous nuclear export mediated by nuclear export signal, and it exhibits few DNA-binding properties. Virus infection but not IFN treatment induces phosphorylation of IRF-3 on specific serine residues, thereby allowing it to complex with the co-activator CBP/p300 with simultaneous nuclear translocation and its specific DNA binding. We also show that a dominant-negative mutant of IRF-3 could inhibit virus-induced activation of chromosomal type I IFN genes and ISGs. These findings suggest that IRF-3 plays an important role in the virus-inducible primary activation of type I IFN and IFN-responsive genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • Cell Line
  • Cell Nucleus / metabolism
  • Cell Nucleus / virology
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Histone Acetyltransferases
  • Humans
  • Interferon Regulatory Factor-3
  • Interferon Type I / genetics
  • Interferon Type I / metabolism*
  • Interferon Type I / physiology
  • Mice
  • Molecular Sequence Data
  • Newcastle disease virus / physiology
  • Nuclear Receptor Coactivator 3
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism*
  • Transcription Factors / biosynthesis
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation*
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Interferon Type I
  • Irf3 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Histone Acetyltransferases
  • NCOA3 protein, human
  • Ncoa3 protein, mouse
  • Nuclear Receptor Coactivator 3