IRF7 explained

Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription factors.

Function

IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. IRF7 has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including the type I interferon genes. In particular, IRF7 regulates many interferon-alpha genes.^[1] Constitutive expression of IRF7 is largely restricted to lymphoid tissue, largely plasmacytoid dendritic cells, whereas IRF7 is inducible in many tissues. Multiple IRF7 transcript variants have been identified, although the functional consequences of these have not yet been established.^[2]

The IRF7 pathway was shown to be silenced in some metastatic breast cancer cell lines, which may help the cells avoid the host immune response.^[3] Restoring IRF7 to these cell lines reduced metastases and increased host survival time in animal models.

The IRF7 gene and product were shown to be defective in a patient with severe susceptibility to H1N1 influenza, while susceptibility to other viral diseases such as CMV, RSV, and parainfluenza was unaffected.^[4]

Interactions

IRF7 has been shown to interact with IRF3.^[5] Also, IRF7 has been shown to interact with Aryl Hydrocarbon Receptor Interacting Protein (AIP), which is a negative regulator for the antiviral pathway.^[6]

See also

• Interferon regulatory factors

Further reading

• Ning S, Pagano JS, Barber GN . IRF7: activation, regulation, modification and function . Genes and Immunity . 12 . 6 . 399–414 . September 2011 . 21490621 . 4437765 . 10.1038/gene.2011.21 .
• Pitha PM, Au WC, Lowther W, Juang YT, Schafer SL, Burysek L, Hiscott J, Moore PA . Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth . Biochimie . 80 . 8–9 . 651–8 . 1999 . 9865487 . 10.1016/S0300-9084(99)80018-2 . free .
• Zhang L, Pagano JS . Structure and function of IRF-7 . Journal of Interferon & Cytokine Research . 22 . 1 . 95–101 . January 2002 . 11846980 . 10.1089/107999002753452700 .
• Zhang L, Pagano JS . IRF-7, a new interferon regulatory factor associated with Epstein-Barr virus latency . Molecular and Cellular Biology . 17 . 10 . 5748–57 . October 1997 . 9315633 . 232423 . 10.1128/MCB.17.10.5748.
• Wathelet MG, Lin CH, Parekh BS, Ronco LV, Howley PM, Maniatis T . Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo . Molecular Cell . 1 . 4 . 507–18 . March 1998 . 9660935 . 10.1016/S1097-2765(00)80051-9 . free .
• Au WC, Moore PA, LaFleur DW, Tombal B, Pitha PM . Characterization of the interferon regulatory factor-7 and its potential role in the transcription activation of interferon A genes . The Journal of Biological Chemistry . 273 . 44 . 29210–7 . October 1998 . 9786932 . 10.1074/jbc.273.44.29210 . free .
• Lu R, Au WC, Yeow WS, Hageman N, Pitha PM . Regulation of the promoter activity of interferon regulatory factor-7 gene. Activation by interferon and silencing by hypermethylation . The Journal of Biological Chemistry . 275 . 41 . 31805–12 . October 2000 . 10924517 . 10.1074/jbc.M005288200 . free .
• Paris MJ, Williams BR . Characterization of a 500-kb contig spanning the region between c-Ha-Ras and MUC2 on chromosome 11p15.5 . Genomics . 69 . 2 . 196–202 . October 2000 . 11031102 . 10.1006/geno.2000.6339 .
• Marié I, Smith E, Prakash A, Levy DE . Phosphorylation-induced dimerization of interferon regulatory factor 7 unmasks DNA binding and a bipartite transactivation domain . Molecular and Cellular Biology . 20 . 23 . 8803–14 . December 2000 . 11073981 . 86519 . 10.1128/MCB.20.23.8803-8814.2000 .
• Smith EJ, Marié I, Prakash A, García-Sastre A, Levy DE . IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein . The Journal of Biological Chemistry . 276 . 12 . 8951–7 . March 2001 . 11124948 . 10.1074/jbc.M008717200 . free .
• Au WC, Yeow WS, Pitha PM . Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3 . Virology . 280 . 2 . 273–82 . February 2001 . 11162841 . 10.1006/viro.2000.0782 . free .
• Lu R, Moore PA, Pitha PM . Stimulation of IRF-7 gene expression by tumor necrosis factor alpha: requirement for NFkappa B transcription factor and gene accessibility . The Journal of Biological Chemistry . 277 . 19 . 16592–8 . May 2002 . 11877397 . 10.1074/jbc.M111440200 . free .
• Morin P, Bragança J, Bandu MT, Lin R, Hiscott J, Doly J, Civas A . Preferential binding sites for interferon regulatory factors 3 and 7 involved in interferon-A gene transcription . Journal of Molecular Biology . 316 . 5 . 1009–22 . March 2002 . 11884139 . 10.1006/jmbi.2001.5401 .
• Caillaud A, Prakash A, Smith E, Masumi A, Hovanessian AG, Levy DE, Marié I . Acetylation of interferon regulatory factor-7 by p300/CREB-binding protein (CBP)-associated factor (PCAF) impairs its DNA binding . The Journal of Biological Chemistry . 277 . 51 . 49417–21 . December 2002 . 12374802 . 10.1074/jbc.M207484200 . free .
• Izmailova E, Bertley FM, Huang Q, Makori N, Miller CJ, Young RA, Aldovini A . HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages . Nature Medicine . 9 . 2 . 191–7 . February 2003 . 12539042 . 10.1038/nm822 . 26145639 .
• Yang H, Lin CH, Ma G, Baffi MO, Wathelet MG . Interferon regulatory factor-7 synergizes with other transcription factors through multiple interactions with p300/CBP coactivators . The Journal of Biological Chemistry . 278 . 18 . 15495–504 . May 2003 . 12604599 . 10.1074/jbc.M212940200 . free .
• Ning S, Hahn AM, Huye LE, Pagano JS . Interferon regulatory factor 7 regulates expression of Epstein-Barr virus latent membrane protein 1: a regulatory circuit . Journal of Virology . 77 . 17 . 9359–68 . September 2003 . 12915551 . 187426 . 10.1128/JVI.77.17.9359-9368.2003 .
• Fitzgerald KA, Rowe DC, Barnes BJ, Caffrey DR, Visintin A, Latz E, Monks B, Pitha PM, Golenbock DT . LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF . The Journal of Experimental Medicine . 198 . 7 . 1043–55 . October 2003 . 14517278 . 2194210 . 10.1084/jem.20031023 .
• Lin R, Noyce RS, Collins SE, Everett RD, Mossman KL . The herpes simplex virus ICP0 RING finger domain inhibits IRF3- and IRF7-mediated activation of interferon-stimulated genes . Journal of Virology . 78 . 4 . 1675–84 . February 2004 . 14747533 . 369457 . 10.1128/JVI.78.4.1675-1684.2004 .

Notes and References

1. Marié I, Durbin JE, Levy DE . Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7 . The EMBO Journal . 17 . 22 . 6660–9 . November 1998 . 9822609 . 1171011 . 10.1093/emboj/17.22.6660 .
2. Web site: Entrez Gene: IRF7 interferon regulatory factor 7.
3. Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Nature Medicine. 18. 8. 1224–1231. Bidwell. 2012. 10.1038/nm.2830. 22820642. 6727932.
4. Ciancanelli MJ, Huang SX, Luthra P, Garner H, Itan Y, Volpi S, Lafaille FG, Trouillet C, Schmolke M, Albrecht RA, Israelsson E, Lim HK, Casadio M, Hermesh T, Lorenzo L, Leung LW, Pedergnana V, Boisson B, Okada S, Picard C, Ringuier B, Troussier F, Chaussabel D, Abel L, Pellier I, Notarangelo LD, García-Sastre A, Basler CF, Geissmann F, Zhang SY, Snoeck HW, Casanova JL . Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency . Science . 348 . 6233 . 448–53 . April 2015 . 25814066 . 4431581 . 10.1126/science.aaa1578 .
5. Au WC, Yeow WS, Pitha PM . Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3 . Virology . 280 . 2 . 273–82 . February 2001 . 11162841 . 10.1006/viro.2000.0782 . free .
6. Zhou Q, Lavorgna A, Bowman M, Hiscott J, Harhaj EW . Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon . The Journal of Biological Chemistry . 290 . 23 . 14729–39 . June 2015 . 25911105 . 10.1074/jbc.M114.633065 . 4505538 . free .