Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction

M Sato; H Suemori; N Hata; M Asagiri; K Ogasawara; K Nakao; T Nakaya; M Katsuki; S Noguchi; N Tanaka; T Taniguchi

doi:10.1016/s1074-7613(00)00053-4

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.

Authors

M Sato¹, H Suemori, N Hata, M Asagiri, K Ogasawara, K Nakao, T Nakaya, M Katsuki, S Noguchi, N Tanaka, T Taniguchi

Affiliation

¹ Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Japan.

PMID: 11070172
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