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Gene Review

Irf7  -  interferon regulatory factor 7

Mus musculus

Synonyms: IRF-7, Interferon regulatory factor 7
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Disease relevance of Irf7


High impact information on Irf7

  • In these cells, a normal profile of IFN-alpha/beta mRNA induction can be achieved by coexpressing both IRF-3 and IRF-7 [3].
  • The kinase activity of IRAK-1 was necessary for transcriptional activation of IRF7 [4].
  • Whereas, IFN-inducible genes (2'5'-oligo(A) synthetase, IRF7, and ISG15) were expressed not only in macrophages but also in other F4/80-negative cells [5].
  • Two members of the IFN regulatory factor (IRF) family of transcription factors, IRF-5 and IRF-7, interact with MyD88 and induce proinflammatory cytokines and type I IFNs, respectively [6].
  • Transforming growth factor beta/Smad3 signaling regulates IRF-7 function and transcriptional activation of the beta interferon promoter [7].

Biological context of Irf7

  • We found, however, heightened responses to IFN-alpha/beta in NOD versus B6 as demonstrated by increased type 1 IFN target gene expression, for example, IRF-7, in NOD DC and macrophages [8].
  • Thus, all elements of IFN responses, whether the systemic production of IFN in innate immunity or the local action of IFN from plasmacytoid dendritic cells in adaptive immunity, are under the control of IRF-7 [9].
  • In the brain, spleen, and liver or cultured glial and spleen cells, IRF-7 but not IRF-9 gene expression increased with delayed kinetics in the absence of STAT1 but not STAT2 following LCMV infection or IFN-alpha treatment, respectively [1].
  • Here, we report a comprehensive structure-activity examination of potential IRF7 phosphorylation sites through analysis of mutant proteins in which specific serine residues were altered to alanine or aspartate [10].
  • The ISGF3 complex also participates in the virus-induced alpha/beta interferon (IFN-alpha/beta) gene amplification cascade by up-regulating IRF-7 gene expression [11].

Anatomical context of Irf7


Associations of Irf7 with chemical compounds

  • Clusters of serine residues located in the carboxyl-terminal regulatory domain of IRF7 are putative targets of virus-activated kinases [10].
  • Impairment of interferon-induced IRF-7 gene expression due to inhibition of ISGF3 formation by trichostatin A [11].

Regulatory relationships of Irf7

  • Consistent with the regulation by Smad3, the transcriptional activity of IRF-7 depended on and was regulated by TGF-beta signaling [7].
  • We also provide evidence that the LPS/TLR4 signaling activates IRF-7 to induce IFN-beta, if IRF-7 is induced by IFNs prior to LPS simulation [14].

Other interactions of Irf7

  • Consistently, Irf7-/- mice are more vulnerable than Myd88-/- mice to viral infection, and this correlates with a marked decrease in serum IFN levels, indicating the importance of the IRF-7-dependent induction of systemic IFN responses for innate antiviral immunity [9].
  • Furthermore, robust induction of IFN production by activation of the TLR9 subfamily in plasmacytoid dendritic cells is entirely dependent on IRF-7, and this MyD88-IRF-7 pathway governs the induction of CD8+ T-cell responses [9].
  • We found that IFN produced locally in the respiratory tract of influenza virus-infected mice displayed characteristics of positive feedback, including Stat1-dependent induction of IRF7 and IFN gene expression [12].
  • Unlike the IRF-3 gene, the IRF-7 gene is induced by IFNs through activation of the ISGF3 transcription factor, and IRF-7 undergoes virus-induced nuclear translocation [15].
  • Overall, under the conditions of our experiments, IRF-3 had good activity for T cells, IRF-7 had good activity for both antibody and T cells, and IRF-1 had good activity for antibody [13].

Analytical, diagnostic and therapeutic context of Irf7


  1. Differential regulation of interferon regulatory factor (IRF)-7 and IRF-9 gene expression in the central nervous system during viral infection. Ousman, S.S., Wang, J., Campbell, I.L. J. Virol. (2005) [Pubmed]
  2. Interferon regulatory factor 7 is associated with Epstein-Barr virus-transformed central nervous system lymphoma and has oncogenic properties. Zhang, L., Zhang, J., Lambert, Q., Der, C.J., Del Valle, L., Miklossy, J., Khalili, K., Zhou, Y., Pagano, J.S. J. Virol. (2004) [Pubmed]
  3. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction. Sato, M., Suemori, H., Hata, N., Asagiri, M., Ogasawara, K., Nakao, K., Nakaya, T., Katsuki, M., Noguchi, S., Tanaka, N., Taniguchi, T. Immunity (2000) [Pubmed]
  4. Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction. Uematsu, S., Sato, S., Yamamoto, M., Hirotani, T., Kato, H., Takeshita, F., Matsuda, M., Coban, C., Ishii, K.J., Kawai, T., Takeuchi, O., Akira, S. J. Exp. Med. (2005) [Pubmed]
  5. Toll-like receptor-independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation. Okabe, Y., Kawane, K., Akira, S., Taniguchi, T., Nagata, S. J. Exp. Med. (2005) [Pubmed]
  6. Negative regulation of Toll-like-receptor signaling by IRF-4. Negishi, H., Ohba, Y., Yanai, H., Takaoka, A., Honma, K., Yui, K., Matsuyama, T., Taniguchi, T., Honda, K. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  7. Transforming growth factor beta/Smad3 signaling regulates IRF-7 function and transcriptional activation of the beta interferon promoter. Qing, J., Liu, C., Choy, L., Wu, R.Y., Pagano, J.S., Derynck, R. Mol. Cell. Biol. (2004) [Pubmed]
  8. Heightened Interferon-{alpha}/beta Response Causes Myeloid Cell Dysfunction and Promotes T1D Pathogenesis in NOD Mice. Peng, R.H., Paek, E., Xia, C.Q., Tennyson, N., Clare-Salzler, M.J. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  9. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Honda, K., Yanai, H., Negishi, H., Asagiri, M., Sato, M., Mizutani, T., Shimada, N., Ohba, Y., Takaoka, A., Yoshida, N., Taniguchi, T. Nature (2005) [Pubmed]
  10. Regulatory serine residues mediate phosphorylation-dependent and phosphorylation-independent activation of interferon regulatory factor 7. Caillaud, A., Hovanessian, A.G., Levy, D.E., Marié, I.J. J. Biol. Chem. (2005) [Pubmed]
  11. Impairment of interferon-induced IRF-7 gene expression due to inhibition of ISGF3 formation by trichostatin A. Génin, P., Morin, P., Civas, A. J. Virol. (2003) [Pubmed]
  12. Tissue-specific positive feedback requirements for production of type I interferon following virus infection. Prakash, A., Smith, E., Lee, C.K., Levy, D.E. J. Biol. Chem. (2005) [Pubmed]
  13. Regulation of DNA-raised immune responses by cotransfected interferon regulatory factors. Sasaki, S., Amara, R.R., Yeow, W.S., Pitha, P.M., Robinson, H.L. J. Virol. (2002) [Pubmed]
  14. Essential role of IRF-3 in lipopolysaccharide-induced interferon-beta gene expression and endotoxin shock. Sakaguchi, S., Negishi, H., Asagiri, M., Nakajima, C., Mizutani, T., Takaoka, A., Honda, K., Taniguchi, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  15. Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7. Sato, M., Hata, N., Asagiri, M., Nakaya, T., Taniguchi, T., Tanaka, N. FEBS Lett. (1998) [Pubmed]
  16. Candidate genes associated with tumor regression mediated by intratumoral IL-12 electroporation gene therapy. Li, S., Xia, X., Mellieon, F.M., Liu, J., Steele, S. Mol. Ther. (2004) [Pubmed]
  17. Super-activated interferon-regulatory factors can enhance plasmid immunization. Bramson, J.L., Dayball, K., Hall, J.R., Millar, J.B., Miller, M., Wan, Y.H., Lin, R., Hiscott, J. Vaccine (2003) [Pubmed]
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