Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes.

Abstract

A family of interferon (IFN) regulatory factors (IRFs) The virus-induced expression of interferon (IFN) genes in infected cells involves interplay of several constitutively expressed and virus-activated transcriptional factors (1). Two of these factors binding to the virus-inducible element of the IFN-3 gene have been proposed to play a crucial role in the regulation of expression of IFN-a and IFN-,3 genes. Interferon regulatory factor 1 (IRF-1) was shown to act as an activator, and the closely related IRF-2 was a repressor (2). It was proposed that induction of the IFN-,3 gene was the result of the removal of repressor IRF-2 and the subsequent binding of the activator IRF-1 (3). Several observations supported this model. Expression of IRF-1 was found to be upregulated in virus-infected cells. The IRF-1 binding sites were identified in the IFN-3 gene promoter region and reporter plasmids with multiple repeats of the AAGTGA hexanucleotides (which are the strong IRF-1 binding site) were inducible by overexpression of IRF-1. This transactivation could be repressed by (2). In embryonal carcinoma cells, overexpression of IRF-1 induced both the transfected and the endogenous IFN-a and -,B genes (4). Moreover, a decrease in IFN-,B induction was observed in cells expressing the IRF-1 antisense mRNA (5).

Fish virus-induced interferon exerts antiviral function through Stat1 pathway

“…IRF3 and IRF7 seem to play similar roles in regulation of type III IFNs (Ank et al, 2008). However, our results showed that both fish IRF3 and IRF7 are induced by virus infection and IFN treatment through the Stat1 pathway, whereas in mammals, IRF3 is constitutively expressed and not induced in virus-infected or IFNtreated cells (Au et al, 1995). Thus, the IFN-inducible nature of fish IFN suggests a positive feedback loop in the regulation of itself, and there are clear discrepancies in the positive feedback regulation of IFN family members between fish and mammals.…”

Regulation of IFN‐α/β genes: evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN‐α/β

“…In a transient transfection assay using IRF-1 -/-p48 -/-dKO EFs, mutations in the IRF-E present within the IFN promoters markedly reduced induction by NDV (Y.K, unpublished data). This may suggest that other IRF family members, such as ICSBP (Driggers et al 1990), LSIRF (Matsuyama et al 1995) or IRF-3 (Au et al 1995) play a role in the induction of the IFN genes. After the completion of this work, Yoneyama et al (1996) reported a role for p48 in IFN gene induction by transfecting a dominant-negative form of p48 in a cultured mouse cell line; their results are essentially consistent with ours.…”

The protein kinase IKKε can inhibit HCV expression independently of IFN and its own expression is downregulated in HCV-infected livers

“…In addition to ISG15, a known IRF3-induced gene, 58 the transcriptome contains the E2-(UbcH8) ligase and E3-CEB1/HERC5 ligase and the USP18 protease. Moreover, the IKK⑀ transcriptome also contains the RIG-I, ISG56, ISG54, STAT1, and MxA genes, which can be ISG15 targets.…”