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Gene Review

IFNA1  -  interferon, alpha 1

Homo sapiens

Synonyms: IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, ...
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Disease relevance of IFNA1


Psychiatry related information on IFNA1


High impact information on IFNA1

  • Consequently, the role of IFN-alpha/beta in the pathogenesis of autoimmunity remains at the forefront of scientific inquiry and has begun to illuminate the mechanisms by which these molecules promote or inhibit systemic and organ-specific autoimmune diseases [10].
  • Certain CpG motifs (CpG-A) are especially potent at activating NK cells and inducing IFN-alpha production by PDCs, while other motifs (CpG-B) are especially potent B cell activators [11].
  • After binding to specific receptors on the surface of infected cells, IFN-alpha/beta has the potential to trigger the activation of multiple noncytolytic intracellular antiviral pathways that can target many steps in the viral life cycle, thereby limiting the amplification and spread of the virus and attenuating the infection [12].
  • In addition to IFN-alpha/beta, a wide range of other innate cytokines can mediate biological functions regulating the NK cell responses of cytotoxicity, proliferation, and gamma interferon (IFN-gamma) production [13].
  • Type I interferon (IFN-alpha and IFN-beta) is secreted by virus-infected cells [14].

Chemical compound and disease context of IFNA1


Biological context of IFNA1

  • Binding of interferons IFN-alpha and IFN-gamma to their cell surface receptors promptly induces tyrosine phosphorylation of latent cytoplasmic transcriptional activators (or Stat proteins, for signal transducers and activators of transcription) [19].
  • Overall, our results reveal a wealth of new information regarding IFN/STAT-binding targets and also fundamental insights into mechanisms of regulation of gene expression in different cell states [20].
  • Interferon (IFN) gamma, a cardinal proinflammatory cytokine, induces expression of the gene products of the class II locus of the major histocompatibility complex (MHC), whereas IFN-alpha or -beta suppresses MHC class II expression [21].
  • Staphylococcal enterotoxin A (SEA) stimulated cord cell IFN gamma production at low cell densities; nevertheless, adult cells produced more IFN in response to SEA 1,341 +/- 350 U/ml) than cord cells (350 +/- 33 U/ml) [22].
  • Upregulation of L-selectin surface density in IFN-alpha-treated Daudi B cells correlated directly with an increase in L-selectin mRNA steady state levels and enhanced L-selectin-dependent binding to a carbohydrate-based ligand, phosphomonoester core polysaccharide [23].

Anatomical context of IFNA1

  • Analysis of the profile of IFNA genes expressed in virus-stimulated PDC, monocytes and MDDC demonstrated that each population expressed IFNA1 as the major subtype but that the range of the subtypes expressed in PDC was broader, with some donor and stimulus-dependent variability [24].
  • Viral multiplication was not inhibited by recombinant IFN-alpha/beta in cell lines from the two individuals [25].
  • We report here striking qualitative and quantitative differences in the intracellular response of human fibroblasts to IFN-gamma compared with IFN-alpha and IFN-beta [26].
  • Furthermore, restoration of ISG15 conjugation in protein ISGylation-defective K562 cells increases IFN-stimulated promoter activity [27].
  • Interferon alpha (IFN-alpha) induces significant antiretroviral activities that affect the ability of human immunodeficiency virus (HIV) to infect and replicate in its principal target cells, CD4+ T cells and macrophages [1].

Associations of IFNA1 with chemical compounds

  • ISG15 is one of the most strongly induced genes upon viral infection, type I interferon (IFN) stimulation, and lipopolysaccharide (LPS) stimulation [27].
  • 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 [1].
  • Both IFN-gamma and type I IFNs (IFN-alpha or IFN-beta) induced 2'-5' oligoadenylate synthetase mRNA and enzyme activity in SMC cultures, but with concentration dependence and time course that may not account for all of IFN-gamma's cytostatic effect on SMC [28].
  • Regardless of this, the antiviral activities of both IFN-alpha and IFN-gamma were attenuated by SB203580 [29].
  • When analyzed by NaDodSO4/polyacrylamide gel electrophoresis the bulk of IFN activity not destroyed by NaDodSO4 treatment was recovered from two peaks with apparent molecular weights of 20,000 and 25,000 [30].

Physical interactions of IFNA1

  • Importantly, the comparison of STAT1-binding sites upon interferon (IFN)-gamma and IFN-alpha treatments revealed dramatic changes in binding locations between the two treatments [20].
  • The IFNAR chain interacts with both IFN-alpha 2 and IFN-beta, as demonstrated by cross-linking [31].
  • Antibodies against a peptide with the CR2 binding sequence on C3d react with a peptide carrying the IFN alpha CR2 binding motif (residues 92-99) and with recombinant IFN alpha [32].
  • A maximal increase in TNF binding was seen after about 6 to 12 hr of incubation with IFN [33].
  • We demonstrate that IFN-alpha will induce the binding of IRF-1 and Stat3 to the respective motifs [34].

Enzymatic interactions of IFNA1

  • Using these, we have identified tyk2 as a 134-kDa protein which is rapidly and transiently phosphorylated on tyrosine in response to IFN-alpha/beta and possesses an inducible kinase activity when tested in vitro [35].
  • Type I interferon (IFN) stimulates transcription through a heteromeric transcription factor that contains tyrosine-phosphorylated STAT2 [36].
  • Analysis of phosphopeptide binding analysis suggests that Stat4 does not interact directly with tyrosine-phosphorylated amino acid residues within the cytoplasmic domains of either of the subunits of the IFN-alpha receptor complex [37].
  • Interferon (IFN) induces gene expression by phosphorylating latent transcription factors of the STAT family [38].
  • Three sequence-tagged site markers in the region bordered by HIFN alpha and D9S171 were used to further map the deleted region by multiplex polymerase chain reaction with the HIFN gamma maker (on chromosome 12) as a control for amplification [39].

Regulatory relationships of IFNA1

  • Interferon (IFN) activates the signal transducer and activator of transcription (STAT) pathway to regulate immune responses [40].
  • Both are IFN dependent and abrogated by a monoclonal antibody which blocks IFNAR action [31].
  • Transient overexpression of IRF9 reproduced the drug-resistance phenotype and induced expression of IFN-responsive genes [41].
  • When macrophages were pretreated with low doses of IFN-gamma and then stimulated with IFN-alpha, clearly enhanced formation of specific transcription factor complexes was detected [42].
  • In turn, the autocrine production of IFN-beta induces the IFN-stimulated genes that contain binding sites for activated STATs in their promoters [43].

Other interactions of IFNA1


Analytical, diagnostic and therapeutic context of IFNA1


  1. 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]
  2. 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]
  3. Eradication of cultured human melanoma cells by immune interferon and leukocytes. Tyring, S.K., Klimpel, G., Brysk, M., Gupta, V., Stanton, G.J., Fleischmann, W.R., Baron, S. J. Natl. Cancer Inst. (1984) [Pubmed]
  4. Heterogeneity of the induction of HLA-DR expression by human immune interferon on glioma cell lines and their clones. Piguet, V., Carrel, S., Diserens, A.C., Mach, J.P., de Tribolet, N. J. Natl. Cancer Inst. (1986) [Pubmed]
  5. Oxidative stress inhibits IFN-alpha-induced antiviral gene expression by blocking the JAK-STAT pathway. Di Bona, D., Cippitelli, M., Fionda, C., Cammà, C., Licata, A., Santoni, A., Craxì, A. J. Hepatol. (2006) [Pubmed]
  6. Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells. Plumlee, C.R., Lazaro, C.A., Fausto, N., Polyak, S.J. Virol. J. (2005) [Pubmed]
  7. Wild-type measles virus infection in human CD46/CD150-transgenic mice: CD11c-positive dendritic cells establish systemic viral infection. Shingai, M., Inoue, N., Okuno, T., Okabe, M., Akazawa, T., Miyamoto, Y., Ayata, M., Honda, K., Kurita-Taniguchi, M., Matsumoto, M., Ogura, H., Taniguchi, T., Seya, T. J. Immunol. (2005) [Pubmed]
  8. Anti-viral protein APOBEC3G is induced by interferon-alpha stimulation in human hepatocytes. Tanaka, Y., Marusawa, H., Seno, H., Matsumoto, Y., Ueda, Y., Kodama, Y., Endo, Y., Yamauchi, J., Matsumoto, T., Takaori-Kondo, A., Ikai, I., Chiba, T. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  9. Combination therapy with interferon alpha and beta to chronic hepatitis C. Horiike, N., Hino, H., Tanaka, Y., Miyaoka, H., Miki, S., Yamashita, S., Matsuura, B., Kubo, Y., Ikeda, Y., Akbar, S.M., Masumoto, T., Michitaka, K., Onji, M. Oncol. Rep. (2003) [Pubmed]
  10. Type I interferons (alpha/beta) in immunity and autoimmunity. Theofilopoulos, A.N., Baccala, R., Beutler, B., Kono, D.H. Annu. Rev. Immunol. (2005) [Pubmed]
  11. CpG motifs in bacterial DNA and their immune effects. Krieg, A.M. Annu. Rev. Immunol. (2002) [Pubmed]
  12. Noncytolytic control of viral infections by the innate and adaptive immune response. Guidotti, L.G., Chisari, F.V. Annu. Rev. Immunol. (2001) [Pubmed]
  13. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Biron, C.A., Nguyen, K.B., Pien, G.C., Cousens, L.P., Salazar-Mather, T.P. Annu. Rev. Immunol. (1999) [Pubmed]
  14. Cellular responses to interferon-gamma. Boehm, U., Klamp, T., Groot, M., Howard, J.C. Annu. Rev. Immunol. (1997) [Pubmed]
  15. Interferon alpha activates NF-kappaB in JAK1-deficient cells through a TYK2-dependent pathway. Yang, C.H., Murti, A., Valentine, W.J., Du, Z., Pfeffer, L.M. J. Biol. Chem. (2005) [Pubmed]
  16. A monoclonal antibody to recombinant human IFN-alpha receptor inhibits biologic activity of several species of human IFN-alpha, IFN-beta, and IFN-omega. Detection of heterogeneity of the cellular type I IFN receptor. Benoit, P., Maguire, D., Plavec, I., Kocher, H., Tovey, M., Meyer, F. J. Immunol. (1993) [Pubmed]
  17. Differential replication of human immunodeficiency virus type 1 in CD8- and CD8+ subsets of natural killer cells: relationship to cytokine production pattern. Tóth, F.D., Mosborg-Petersen, P., Kiss, J., Aboagye-Mathiesen, G., Zdravkovic, M., Hager, H., Ebbesen, P. J. Virol. (1993) [Pubmed]
  18. 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]
  19. Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Shuai, K., Ziemiecki, A., Wilks, A.F., Harpur, A.G., Sadowski, H.B., Gilman, M.Z., Darnell, J.E. Nature (1993) [Pubmed]
  20. Global changes in STAT target selection and transcription regulation upon interferon treatments. Hartman, S.E., Bertone, P., Nath, A.K., Royce, T.E., Gerstein, M., Weissman, S., Snyder, M. Genes Dev. (2005) [Pubmed]
  21. 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]
  22. Decreased production of interferon-gamma by human neonatal cells. Intrinsic and regulatory deficiencies. Wilson, C.B., Westall, J., Johnston, L., Lewis, D.B., Dower, S.K., Alpert, A.R. J. Clin. Invest. (1986) [Pubmed]
  23. Interferon-alpha induces the expression of the L-selectin homing receptor in human B lymphoid cells. Evans, S.S., Collea, R.P., Appenheimer, M.M., Gollnick, S.O. J. Cell Biol. (1993) [Pubmed]
  24. Comparative analysis of IRF and IFN-alpha expression in human plasmacytoid and monocyte-derived dendritic cells. Izaguirre, A., Barnes, B.J., Amrute, S., Yeow, W.S., Megjugorac, N., Dai, J., Feng, D., Chung, E., Pitha, P.M., Fitzgerald-Bocarsly, P. J. Leukoc. Biol. (2003) [Pubmed]
  25. Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Dupuis, S., Jouanguy, E., Al-Hajjar, S., Fieschi, C., Al-Mohsen, I.Z., Al-Jumaah, S., Yang, K., Chapgier, A., Eidenschenk, C., Eid, P., Al Ghonaium, A., Tufenkeji, H., Frayha, H., Al-Gazlan, S., Al-Rayes, H., Schreiber, R.D., Gresser, I., Casanova, J.L. Nat. Genet. (2003) [Pubmed]
  26. A unique set of polypeptides is induced by gamma interferon in addition to those induced in common with alpha and beta interferons. Weil, J., Epstein, C.J., Epstein, L.B., Sedmak, J.J., Sabran, J.L., Grossberg, S.E. Nature (1983) [Pubmed]
  27. Protein ISGylation modulates the JAK-STAT signaling pathway. Malakhova, O.A., Yan, M., Malakhov, M.P., Yuan, Y., Ritchie, K.J., Kim, K.I., Peterson, L.F., Shuai, K., Zhang, D.E. Genes Dev. (2003) [Pubmed]
  28. Immune interferon inhibits proliferation and induces 2'-5'-oligoadenylate synthetase gene expression in human vascular smooth muscle cells. Warner, S.J., Friedman, G.B., Libby, P. J. Clin. Invest. (1989) [Pubmed]
  29. p38 MAP kinase is required for STAT1 serine phosphorylation and transcriptional activation induced by interferons. Goh, K.C., Haque, S.J., Williams, B.R. EMBO J. (1999) [Pubmed]
  30. Purification of two subspecies of human gamma (immune) interferon. Yip, Y.K., Barrowclough, B.S., Urban, C., Vilcek, J. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  31. 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]
  32. Epstein Barr virus/complement C3d receptor is an interferon alpha receptor. Delcayre, A.X., Salas, F., Mathur, S., Kovats, K., Lotz, M., Lernhardt, W. EMBO J. (1991) [Pubmed]
  33. Interferon-gamma enhances expression of cellular receptors for tumor necrosis factor. Tsujimoto, M., Yip, Y.K., Vilcek, J. J. Immunol. (1986) [Pubmed]
  34. IFN-alpha induces the human IL-10 gene by recruiting both IFN regulatory factor 1 and Stat3. Ziegler-Heitbrock, L., Lötzerich, M., Schaefer, A., Werner, T., Frankenberger, M., Benkhart, E. J. Immunol. (2003) [Pubmed]
  35. Activation of the protein tyrosine kinase tyk2 by interferon alpha/beta. Barbieri, G., Velazquez, L., Scrobogna, M., Fellous, M., Pellegrini, S. Eur. J. Biochem. (1994) [Pubmed]
  36. IFN-Stimulated transcription through a TBP-free acetyltransferase complex escapes viral shutoff. Paulson, M., Press, C., Smith, E., Tanese, N., Levy, D.E. Nat. Cell Biol. (2002) [Pubmed]
  37. Recruitment of Stat4 to the human interferon-alpha/beta receptor requires activated Stat2. Farrar, J.D., Smith, J.D., Murphy, T.L., Murphy, K.M. J. Biol. Chem. (2000) [Pubmed]
  38. ISGF3 gamma p48, a specificity switch for interferon activated transcription factors. Bluyssen, A.R., Durbin, J.E., Levy, D.E. Cytokine Growth Factor Rev. (1996) [Pubmed]
  39. Homozygous deletions but no sequence mutations in coding regions of p15 or p16 in human primary bladder tumors. Packenham, J.P., Taylor, J.A., Anna, C.H., White, C.M., Devereux, T.R. Mol. Carcinog. (1995) [Pubmed]
  40. PIAS1 selectively inhibits interferon-inducible genes and is important in innate immunity. Liu, B., Mink, S., Wong, K.A., Stein, N., Getman, C., Dempsey, P.W., Wu, H., Shuai, K. Nat. Immunol. (2004) [Pubmed]
  41. Overexpression of IRF9 confers resistance to antimicrotubule agents in breast cancer cells. Luker, K.E., Pica, C.M., Schreiber, R.D., Piwnica-Worms, D. Cancer Res. (2001) [Pubmed]
  42. Interferons up-regulate STAT1, STAT2, and IRF family transcription factor gene expression in human peripheral blood mononuclear cells and macrophages. Lehtonen, A., Matikainen, S., Julkunen, I. J. Immunol. (1997) [Pubmed]
  43. 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]
  44. 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]
  45. Recruitment of multiple interferon regulatory factors and histone acetyltransferase to the transcriptionally active interferon a promoters. Au, W.C., Pitha, P.M. J. Biol. Chem. (2001) [Pubmed]
  46. Structure of the human immune interferon gene. Gray, P.W., Goeddel, D.V. Nature (1982) [Pubmed]
  47. Inhibition of interferon-inducible gene expression by adenovirus E1A proteins: block in transcriptional complex formation. Kalvakolanu, D.V., Bandyopadhyay, S.K., Harter, M.L., Sen, G.C. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  48. Type I interferons in combination with bacterial stimuli induce apoptosis of monocyte-derived dendritic cells. Lehner, M., Felzmann, T., Clodi, K., Holter, W. Blood (2001) [Pubmed]
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