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Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes.

Interferon regulatory factor (IRF) genes encode DNA-binding proteins that are involved in the innate immune response to infection. Two of these proteins, IRF-3 and IRF-7, serve as direct transducers of virus-mediated signaling and play critical roles in the induction of type I interferon genes. We have now shown that another factor, IRF-5, participates in the induction of interferon A (IFNA) and IFNB genes and can replace the requirement for IRF-7 in the induction of IFNA genes. We demonstrate that, despite the functional similarity, IRF-5 possesses unique characteristics and does not have a redundant role. Thus, 1) activation of IRF-5 by phosphorylation is virus-specific, and its in vivo association with the IFNA promoter can be detected only in cells infected with NDV, not Sendai virus, while both viruses activate IRF-3 and IRF-7, and 2) NDV infection of IRF-5-overexpressing cells preferentially induced the IFNA8 subtype, while IFNA1 was primarily induced in IRF-7 expressing cells. These data indicate that multiple signaling pathways induced by infection may be differentially recognized by members of the IRF family and modulate transcription of individual IFNA genes in a virus and cell type-specific manner.

Pubmed ID: 11303025


  • Barnes BJ
  • Moore PA
  • Pitha PM


The Journal of biological chemistry

Publication Data

June 29, 2001

Associated Grants

  • Agency: NIAID NIH HHS, Id: AII937

Mesh Terms

  • B-Lymphocytes
  • Base Sequence
  • Cell Line
  • Cell Nucleus
  • DNA-Binding Proteins
  • Dendritic Cells
  • HeLa Cells
  • Humans
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factors
  • Interferon-alpha
  • Interferon-beta
  • Lymphoid Tissue
  • Molecular Sequence Data
  • Newcastle disease virus
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • RNA, Messenger
  • Respirovirus
  • Response Elements
  • Species Specificity
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Activation