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Gene Review

IFNB1  -  interferon, beta 1, fibroblast

Homo sapiens

Synonyms: Fibroblast interferon, IFB, IFF, IFN-beta, IFNB, ...
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Disease relevance of IFNB1


Psychiatry related information on IFNB1


High impact information on IFNB1

  • Type I interferon (IFN-alpha and IFN-beta) is secreted by virus-infected cells [10].
  • Conversely, overexpression of MAVS induces the expression of IFN-beta through activation of NF-kappaB and IRF 3, thus boosting antiviral immunity [11].
  • We show that delivery of this nucleosome to the same downstream position to create an accessible IFN-beta core promoter prior to enhanceosome assembly results in major changes in the gene expression program with regard to the temporal pattern and the signal specificity of the transcriptional response [12].
  • Transcriptional activation of the IFN-beta gene in response to virus infection requires the assembly of an enhanceosome, which instructs a recruitment program of chromatin modifiers/remodelers and general transcription factors to the promoter [12].
  • Here, we show that a nucleosome obstructing transcription from the IFN-beta promoter slides in vivo in response to virus infection, thus exposing the previously masked TATA box and the initiation site, a requirement for transcriptional activation [13].

Chemical compound and disease context of IFNB1


Biological context of IFNB1


Anatomical context of IFNB1


Associations of IFNB1 with chemical compounds

  • Furthermore, the enhanced antiviral effect of asialo-IFN-beta was supported by induction of the 2'-5' oligoadenylate synthetase, an indicator of IFN activity, at a level significantly higher than that produced by conventional IFN-beta [2].
  • Because the asialoglycoprotein (ASGP) receptor is specifically expressed in the liver at high density, the ASGP receptor-binding domain was generated within an N-glycosylated human IFN-beta molecule by the removal of sialic acid to direct this cytokine to the liver [2].
  • The antiviral activity induced by poly(I).poly(C) may be a direct effect of this synthetic double-stranded RNA or secondary to the low levels of IFN-beta and IFN-omega produced by infected cells [26].
  • Interestingly, the inhibitory effect was much less pronounced when IFN-beta was added greater than or equal to 1 hr before TNF [27].
  • The major oligosaccharide of the recombinant IFN-beta is remarkably homogeneous with respect to terminal galactose sialylation [28].

Physical interactions of IFNB1


Enzymatic interactions of IFNB1

  • Here, we show that IFN-beta sensitizes glioma cells that harbor the unmethylated MGMT promoter and are resistant to temozolomide [34].
  • Here we demonstrate that gelatinase B proteolytically cleaves IFN-beta, kills its activity, and hence counteracts this cytokine as an antiviral and immunotherapeutic agent [35].
  • The percentage of IFNbeta-stimulated monocytes positive for phosphorylated STAT-1 (pSTAT-1) and the number of IL2- and IL15-stimulated T cells expressing phosphorylated STAT-5 (pSTAT-5) were determined at 0 and 24 h [36].

Regulatory relationships of IFNB1

  • In turn, the autocrine production of IFN-beta induces the IFN-stimulated genes that contain binding sites for activated STATs in their promoters [37].
  • We previously showed that IFN beta inhibited IFN gamma-induced DRA expression at the transcriptional level [38].
  • Upon infection, constitutively expressed NF-kappaB and IRF-3 are activated and likely contribute to the rapid IFN-beta expression [37].
  • Once expressed, IRF-1 may further stimulate the transcription of IFN-beta [37].
  • None of these anti-IFNAR1 mAbs were able to block activity of IFN-beta. mAb 4A7 binds to a domain 1-hIFNAR1-IgG but not to a domain 2-hIFNAR1-IgG, which suggests that its binding region is located in domain 1 [39].

Other interactions of IFNB1

  • Different pathways mediate virus inducibility of the human IFN-alpha 1 and IFN-beta genes [40].
  • Because antigenic typing of the antiviral activity of these LK and MK preparations revealed that LK contained mainly gamma interferon (IFN-gamma), and MK, primarily IFN-beta, we investigated if any of the fibroblast-inhibiting activities could be attributed to human IFN [41].
  • These results suggest that IFN-beta acts downstream of CIITA mRNA accumulation, and acts in part by reducing the functional competence of CIITA for transactivating MHC class II promoters [42].
  • After IFN-beta treatment for 5 min, a tyrosine-phosphorylated protein of approximately 95 kDa (beta-PTyr) is found bound to IFNAR, but can be dissociated by denaturation [19].
  • The inhibitory action of IFN-beta on IL-8 mRNA accumulation was undiminished in the presence of inhibitors of protein synthesis [27].

Analytical, diagnostic and therapeutic context of IFNB1


  1. Genetic and physical map of the interferon region on chromosome 9p. Fountain, J.W., Karayiorgou, M., Taruscio, D., Graw, S.L., Buckler, A.J., Ward, D.C., Dracopoli, N.C., Housman, D.E. Genomics (1992) [Pubmed]
  2. Enhanced inhibition of hepatitis B virus production by asialoglycoprotein receptor-directed interferon. Eto, T., Takahashi, H. Nat. Med. (1999) [Pubmed]
  3. Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro. Kornbluth, R.S., Oh, P.S., Munis, J.R., Cleveland, P.H., Richman, D.D. J. Exp. Med. (1989) [Pubmed]
  4. Involvement of the double-stranded-RNA-dependent kinase PKR in interferon expression and interferon-mediated antiviral activity. Der, S.D., Lau, A.S. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  5. Correlation between interferon (IFN) alpha resistance and deletion of the IFN alpha/beta genes in acute leukemia cell lines suggests selection against the IFN system. Colamonici, O.R., Domanski, P., Platanias, L.C., Diaz, M.O. Blood (1992) [Pubmed]
  6. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Saito, T., Hirai, R., Loo, Y.M., Owen, D., Johnson, C.L., Sinha, S.C., Akira, S., Fujita, T., Gale, M. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  7. siRNA and isRNA: two edges of one sword. Schlee, M., Hornung, V., Hartmann, G. Mol. Ther. (2006) [Pubmed]
  8. Electrophysiological and neuropsychological functions in patients treated with interferon-beta. Liberati, A.M., Biagini, S., Perticoni, G., Ricci, S., D'Alessandro, P., Senatore, M., Cinieri, S. J. Interferon Res. (1990) [Pubmed]
  9. Quality of life during the first 6 months of interferon-beta treatment in patients with MS. Arnoldus, J.H., Killestein, J., Pfennings, L.E., Jelles, B., Uitdehaag, B.M., Polman, C.H. Mult. Scler. (2000) [Pubmed]
  10. Cellular responses to interferon-gamma. Boehm, U., Klamp, T., Groot, M., Howard, J.C. Annu. Rev. Immunol. (1997) [Pubmed]
  11. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Seth, R.B., Sun, L., Ea, C.K., Chen, Z.J. Cell (2005) [Pubmed]
  12. Modifying gene expression programs by altering core promoter chromatin architecture. Lomvardas, S., Thanos, D. Cell (2002) [Pubmed]
  13. Nucleosome sliding via TBP DNA binding in vivo. Lomvardas, S., Thanos, D. Cell (2001) [Pubmed]
  14. Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis. Leaman, D.W., Chawla-Sarkar, M., Vyas, K., Reheman, M., Tamai, K., Toji, S., Borden, E.C. J. Biol. Chem. (2002) [Pubmed]
  15. Increased human immunodeficiency virus (HIV) expression in chronically infected U937 cells upon in vitro differentiation by hydroxyvitamin D3: roles of interferon and tumor necrosis factor in regulation of HIV production. Locardi, C., Petrini, C., Boccoli, G., Testa, U., Dieffenbach, C., Buttò, S., Belardelli, F. J. Virol. (1990) [Pubmed]
  16. Tamoxifen enhances interferon-regulated gene expression in breast cancer cells. Lindner, D.J., Kolla, V., Kalvakolanu, D.V., Borden, E.C. Mol. Cell. Biochem. (1997) [Pubmed]
  17. Interferon-beta from melanoma cells suppresses the proliferations of melanoma cells in an autocrine manner. Satomi, H., Wang, B., Fujisawa, H., Otsuka, F. Cytokine (2002) [Pubmed]
  18. trans activation of type 1 interferon promoters by simian virus 40 T antigen. Hiscott, J., Wong, A., Alper, D., Xanthoudakis, S. Mol. Cell. Biol. (1988) [Pubmed]
  19. Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-alpha and IFN-beta. Abramovich, C., Shulman, L.M., Ratovitski, E., Harroch, S., Tovey, M., Eid, P., Revel, M. EMBO J. (1994) [Pubmed]
  20. Immunoregulatory properties of ISG15, an interferon-induced cytokine. D'Cunha, J., Knight, E., Haas, A.L., Truitt, R.L., Borden, E.C. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  21. Transcriptional inhibition of the interleukin-8 gene by interferon is mediated by the NF-kappa B site. Oliveira, I.C., Mukaida, N., Matsushima, K., Vilcek, J. Mol. Cell. Biol. (1994) [Pubmed]
  22. HLA class I heavy-chain gene promoter elements mediating synergy between tumor necrosis factor and interferons. Johnson, D.R., Pober, J.S. Mol. Cell. Biol. (1994) [Pubmed]
  23. Molecular deletion of 9p sequences in non-small cell lung cancer and malignant mesothelioma. Center, R., Lukeis, R., Dietzsch, E., Gillespie, M., Garson, O.M. Genes Chromosomes Cancer (1993) [Pubmed]
  24. Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Zhao, C., Denison, C., Huibregtse, J.M., Gygi, S., Krug, R.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  25. Natural killer cell activity from hemophiliacs exhibits differential responses to various forms of interferon. Matheson, D.S., Green, B.J., Poon, M.C., Fritzler, M.J., Hoar, D.I., Bowen, T.J. Blood (1986) [Pubmed]
  26. A selective defect of interferon alpha production in human immunodeficiency virus-infected monocytes. Gendelman, H.E., Friedman, R.M., Joe, S., Baca, L.M., Turpin, J.A., Dveksler, G., Meltzer, M.S., Dieffenbach, C. J. Exp. Med. (1990) [Pubmed]
  27. Downregulation of interleukin 8 gene expression in human fibroblasts: unique mechanism of transcriptional inhibition by interferon. Oliveira, I.C., Sciavolino, P.J., Lee, T.H., Vilcek, J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  28. Structure of the carbohydrate moiety of human interferon-beta secreted by a recombinant Chinese hamster ovary cell line. Conradt, H.S., Egge, H., Peter-Katalinic, J., Reiser, W., Siklosi, T., Schaper, K. J. Biol. Chem. (1987) [Pubmed]
  29. Inositol hexakisphosphate kinase 2 mediates growth suppressive and apoptotic effects of interferon-beta in ovarian carcinoma cells. Morrison, B.H., Bauer, J.A., Kalvakolanu, D.V., Lindner, D.J. J. Biol. Chem. (2001) [Pubmed]
  30. Conserved nontypeable Haemophilus influenzae-derived TLR2-binding lipopeptides synergize with IFN-beta to increase cytokine production by resident murine and human alveolar macrophages. Punturieri, A., Copper, P., Polak, T., Christensen, P.J., Curtis, J.L. J. Immunol. (2006) [Pubmed]
  31. Inquiring into the differential action of interferons (IFNs): an IFN-alpha2 mutant with enhanced affinity to IFNAR1 is functionally similar to IFN-beta. Jaitin, D.A., Roisman, L.C., Jaks, E., Gavutis, M., Piehler, J., Van der Heyden, J., Uze, G., Schreiber, G. Mol. Cell. Biol. (2006) [Pubmed]
  32. A peptide mimetic of human interferon (IFN)-beta. Sato, A., Sone, S. Biochem. J. (2003) [Pubmed]
  33. Viral induction of the human beta interferon promoter: modulation of transcription by NF-kappa B/rel proteins and interferon regulatory factors. Garoufalis, E., Kwan, I., Lin, R., Mustafa, A., Pepin, N., Roulston, A., Lacoste, J., Hiscott, J. J. Virol. (1994) [Pubmed]
  34. IFN-beta down-regulates the expression of DNA repair gene MGMT and sensitizes resistant glioma cells to temozolomide. Natsume, A., Ishii, D., Wakabayashi, T., Tsuno, T., Hatano, H., Mizuno, M., Yoshida, J. Cancer Res. (2005) [Pubmed]
  35. Gelatinase B/matrix metalloproteinase-9 cleaves interferon-beta and is a target for immunotherapy. Nelissen, I., Martens, E., Van den Steen, P.E., Proost, P., Ronsse, I., Opdenakker, G. Brain (2003) [Pubmed]
  36. Extracorporeal photopheresis differentially regulates the expression of phosphorylated STAT-1 and STAT-5 in treated monocytes and T cells, respectively. Bladon, J., Taylor, P. Journal of cutaneous medicine and surgery. (2004) [Pubmed]
  37. Selective expression of type I IFN genes in human dendritic cells infected with Mycobacterium tuberculosis. Remoli, M.E., Giacomini, E., Lutfalla, G., Dondi, E., Orefici, G., Battistini, A., Uzé, G., Pellegrini, S., Coccia, E.M. J. Immunol. (2002) [Pubmed]
  38. Inhibition of interferon-gamma-induced major histocompatibility complex class II gene transcription by interferon-beta and type beta 1 transforming growth factor in human astrocytoma cells. Definition of cis-element. Devajyothi, C., Kalvakolanu, I., Babcock, G.T., Vasavada, H.A., Howe, P.H., Ransohoff, R.M. J. Biol. Chem. (1993) [Pubmed]
  39. Structure-function study of the extracellular domain of the human IFN-alpha receptor (hIFNAR1) using blocking monoclonal antibodies: the role of domains 1 and 2. Lu, J., Chuntharapai, A., Beck, J., Bass, S., Ow, A., De Vos, A.M., Gibbs, V., Kim, K.J. J. Immunol. (1998) [Pubmed]
  40. Different pathways mediate virus inducibility of the human IFN-alpha 1 and IFN-beta genes. MacDonald, N.J., Kuhl, D., Maguire, D., Näf, D., Gallant, P., Goswamy, A., Hug, H., Büeler, H., Chaturvedi, M., de la Fuente, J. Cell (1990) [Pubmed]
  41. Gamma interferon is the lymphokine and beta interferon the monokine responsible for inhibition of fibroblast collagen production and late but not early fibroblast proliferation. Duncan, M.R., Berman, B. J. Exp. Med. (1985) [Pubmed]
  42. Interferon (IFN) beta acts downstream of IFN-gamma-induced class II transactivator messenger RNA accumulation to block major histocompatibility complex class II gene expression and requires the 48-kD DNA-binding protein, ISGF3-gamma. Lu, H.T., Riley, J.L., Babcock, G.T., Huston, M., Stark, G.R., Boss, J.M., Ransohoff, R.M. J. Exp. Med. (1995) [Pubmed]
  43. Activation of 2',5'-oligoadenylate synthetase activity on induction of HL-60 leukemia cell differentiation. Schwartz, E.L., Nilson, L.A. Mol. Cell. Biol. (1989) [Pubmed]
  44. Regulation of IFN-alpha/beta, MxA, 2',5'-oligoadenylate synthetase, and HLA gene expression in influenza A-infected human lung epithelial cells. Ronni, T., Matikainen, S., Sareneva, T., Melén, K., Pirhonen, J., Keskinen, P., Julkunen, I. J. Immunol. (1997) [Pubmed]
  45. Retrovirally mediated IFN-beta transduction of macrophages induces resistance to HIV, correlated with up-regulation of RANTES production and down-regulation of C-C chemokine receptor-5 expression. Cremer, I., Vieillard, V., De Maeyer, E. J. Immunol. (2000) [Pubmed]
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