Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction.
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.
Sato
M
M
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Japan.
Suemori
H
H
Hata
N
N
Asagiri
M
M
Ogasawara
K
K
Nakao
K
K
Nakaya
T
T
Katsuki
M
M
Noguchi
S
S
Tanaka
N
N
Taniguchi
T
T
D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004622:Embryo, Mammalian; D005260:Female; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D018390:Gene Targeting; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009522:Newcastle disease virus / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D012190:Retroviridae / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D016899:Interferon-beta