Gene induction pathways mediated by distinct IRFs during viral infection.
During viral infection, interferon-alpha/beta (IFN-alpha/beta) and many IFN-inducible genes are induced to elicit antiviral responses of the host. Using cells with a gene disruption(s) for the IRF family of transcription factors, we provide evidence that these genes, containing similar IRF-binding cis-elements, are classified into distinct groups, based on the gene induction pathway(s). The IFN-beta gene induction is dependent on either IRF-3 or IRF-7, whereas induction of the IFN-alpha gene family is IRF-7-dependent. On the other hand, ISG15, ISG54 and IP-10 are induced by either IRF-3 or IFN stimulated gene factor 3 (ISGF3). We also show that another group of genes is totally dependent on ISGF3. Thus, during viral infection, a given gene responds either directly to a virus or virus-induced IFN-alpha/beta or both through distinct pathways. The differential utilization of these induction pathways for these genes during viral infection may reflect their distinct functional roles in the efficient antiviral response.
Nakaya
T
T
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
Sato
M
M
Hata
N
N
Asagiri
M
M
Suemori
H
H
Noguchi
S
S
Tanaka
N
N
Taniguchi
T
T
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000235:genetics*; D016899:Interferon-beta / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D009521:Newcastle Disease / Q000276:immunology*; D009522:Newcastle disease virus / Q000235:genetics / Q000276:immunology*; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D051017:Apoptosis Regulatory Proteins; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D004268:DNA-Binding Proteins; C484289:IFIT2 protein, human; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; C494228:Isgf3g protein, mouse; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase