Distinct and Essential Roles of Transcription Factors IRF-3 and IRF-7 in Response to Viruses for IFN-alpha/beta Gene Induction

Immunity. 2000 Oct;13(4):539-48. doi: 10.1016/s1074-7613(00)00053-4.

Abstract

Induction of the interferon (IFN)-alpha/beta gene transcription in virus-infected cells is an event central to innate immunity. Mice lacking the transcription factor IRF-3 are more vulnerable to virus infection. In embryonic fibroblasts, virus-induced IFN-alpha/beta gene expression levels are reduced and the spectrum of the IFN-alpha mRNA subspecies altered. Furthermore, cells additionally defective in IRF-7 expression totally fail to induce these genes in response to infections by any of the virus types tested. In these cells, a normal profile of IFN-alpha/beta mRNA induction can be achieved by coexpressing both IRF-3 and IRF-7. These results demonstrate the essential and distinct roles of thetwo factors, which together ensure the transcriptional efficiency and diversity of IFN-alpha/beta genes for the antiviral response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Embryo, Mammalian
  • Female
  • Fibroblasts
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Gene Targeting
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Interferon Type I / biosynthesis*
  • Interferon Type I / deficiency
  • Interferon Type I / genetics*
  • Interferon Type I / physiology
  • Interferon-beta / genetics
  • Interferon-beta / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Newcastle disease virus / genetics
  • Newcastle disease virus / physiology*
  • Promoter Regions, Genetic / immunology
  • RNA, Messenger / biosynthesis
  • Retroviridae / genetics
  • Retroviridae / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Transcription Factors / biosynthesis
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcriptional Activation

Substances

  • DNA-Binding Proteins
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Interferon Type I
  • Irf3 protein, mouse
  • Irf7 protein, mouse
  • RNA, Messenger
  • Transcription Factors
  • Interferon-beta