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