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Molecular and functional analysis of the virus- and interferon-inducible human MxA promoter

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Summary

The virus- and interferon-inducible human MxA (IFI-78k) gene is a homologue of the murine influenza resistance gene Mx1. Three overlapping human cosmid clones covering most of the gene including its promoter region were isolated. Sequencing the 5′ MxA cDNA derived by RT-PCR (reverse transcriptase-polymerase chain reaction) confirmed the most 5′ putative transcriptional start site. The MxA promoter does not contain a TATA or CCAAT box but has three Interferon Stimulated Response Element (ISRE) motifs. Strong induction with type I interferons was demonstrated with a fragment containing only two ISREs in human L132 cells. This induced expression was not adversely affected by 2-aminopurine. However, the promoter showed constitutive expression in transiently or stably transfected murine LM cells.

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References

  1. Aebi M, Fah J, Hurt N, Samuel CE, Thomas D, Bazzigher L, Pavlovic J, Haller O, Staeheli P (1989) cDNA structures and regulation of two interferon-induced human Mx proteins. Mol Cell Biol 9: 5062–5072

    Google Scholar 

  2. Arnheiter H, Haller O (1988) Antiviral state against influenza virus neutralized by microinjection of antibodies to interferon-induced Mx proteins. EMBO J 7: 1315–1320

    Google Scholar 

  3. Asano M, Hayashi M, Yoshida E, Kawade Y, Iwakura Y (1990) Induction of interferon-alpha by interferon-beta, but not of interferon-beta by interferon-alpha, in the mouse. Virology 176: 30–38

    Google Scholar 

  4. Bucher P, Trifonov EN (1986) Compilation and analysis of eukaryotic POL II promoter sequences. Nucleic Acids Res 14: 10009–10026

    Google Scholar 

  5. Chang KC, Goldspink G, Lida J (1990) Studies in the in vivo expression of the influenza resistance gene Mx by in situ hybridisation. Arch Virol 110: 151–164

    Google Scholar 

  6. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159

    Google Scholar 

  7. Dreiding P, Staeheli P, Haller O (1985) Interferon-induced protein Mx accumulates in nuclei of mouse cell expressing resistance to influenza viruses. Virology 149: 192–196

    Google Scholar 

  8. Enoch T, Zinn K, Maniatis T (1986) Activation of the human beta-interferon gene requires an interferon-inducible factor. Mol Cell Biol 6: 801–810

    Google Scholar 

  9. Fan C-M, Maniatis T (1989) Two different virus-inducible elements are required for human beta-interferon gene regulation. EMBO J 8: 101–110

    Google Scholar 

  10. Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132: 6–13

    Google Scholar 

  11. Fourney RM, Miyakoshi J, Day III RS, Paterson MC (1988) Northern blotting: efficient RNA staining and transfer. Focus (Gibco-BRL) 10: 5–7

    Google Scholar 

  12. Friedman RL, Stark GR (1985) Alpha-interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences. Nature 314: 537–639

    Google Scholar 

  13. Fujita T, Shibuya H. Hotta H, Yamanishi K, Taniguchi T (1987) Interferon-beta gene regulation: tandemly repeated sequences of a synthetic 6 bp oligomer function as a virus-inducible enhancer. Cell 49: 357–367

    Google Scholar 

  14. Goetschy JF, Zeller H, Content J, Horisberger MA (1989) Regulation of the interferon-inducible IFI-78K gene, the human equivalent of the murine Mx gene, by interferons, double-stranded RNA, certain cytokines, and viruses. J Virol 63: 2616–2622

    Google Scholar 

  15. Goddbourn S, Maniatis T (1988) Overlapping positive and negative regulatory domains of the human beta-interferon gene. Proc Natl Acad Sci USA 85: 1447–1451

    Google Scholar 

  16. Horisberger MA (1988) The action of recombinant bovine interferons on influenza virus replication correlates with the induction of two Mx-related proteins in bovine cells. Virology 162: 181–186

    Google Scholar 

  17. Horisberger MA (1988) Homologs of the IFN-induced mouse protein in 14 animal species. J Interferon Res 8: S 102

    Google Scholar 

  18. Horisberger MA, Hochkeppel HK (1985) An interferon-induced mouse protein involved in the mechanism of resistance to influenza viruses. J Biol Chem 3: 1730–1733

    Google Scholar 

  19. Horisberger MA, McMaster GK, Zeller H, Wathelet MG, Dellis J, Content J (1990) Cloning and sequence analysis of cDNAs for interferon- and virus-induced human Mx proteins reveal that they contain putative guanine nucleotide-binding sites: functional study of the corresponding gene promoter. J Virol 64: 1171–1181

    Google Scholar 

  20. Horisberger MA, Wathelet M, Szpirer J. Szpirer C, Islam Q, Levan G, Huez G, Content J (1988) cDNA cloning and assignment to chromosome 21 of IFI-78K gene, the human equivalent of murine Mx gene. Somat Cell Mol Genet 14: 123–131

    Google Scholar 

  21. Hug H, Costas M, Staeheli P, Aebi M, Weissmann C (1988) Organization of the murine Mx gene and characterization of its interferon- and virus-inducible promoter. Mol Cell Biol 8: 3065–3079

    Google Scholar 

  22. Jabobsen H (1986) Interferons and antiviral activity. Arzneimittelforschung 36: 512–516

    Google Scholar 

  23. Kadonaga JT. Jones KA, Tijan R (1986) Promoter-specific activation of RNA polymerase II transcription by Spl. Trends Biochem Sci 11: 20–23

    Google Scholar 

  24. Kessler DS, Levy DE, Darnell Jr JE (1988) Two interferon-induced nuclear factors bind a single promoter element in interferon-stimulated genes. Proc Natl Acad Sci USA 85: 8521–8525

    Google Scholar 

  25. Kirchner H (1986) The interferon system as an integral part of the defense system against infections. Antiviral Res 6: 1–17

    Google Scholar 

  26. MacDonald JN et al (1990) Different pathways mediate virus inducibility of the human IFN-alpha 1 and IFN-beta genes. Cell 60: 767–779

    Google Scholar 

  27. Myers JC, Chu ML, Scott F, Clark WJ, Prockop DJ, Ramirez F (1981) Cloning of a cDNA for the pro-alpha 2 chain of human type I collagen. Proc Natl Acad Sci USA 78: 3516–3520

    Google Scholar 

  28. Nikovits W Jr, Mar JH, Ordahl P (1990) Muscle-specific activity of the skeletal troponon I promoter requires interaction between upstream regulatory sequences and elements contained within the first transcribed exon. Mol Cell Biol 10: 3468–3482

    Google Scholar 

  29. Opdenakker G, Cabeza-Arvelaiz Y, Van Damme J (1989) Interaction of interferon with other cytokines. Experientia 45: 513–519

    Google Scholar 

  30. Pavlovic J, Zürcher T, Haller O, Staeheli P (1990) Resistance to influenza virus and vesicular stomatitis virus conferred by expression of human MxA protein. J Virol 64: 3370–3375

    Google Scholar 

  31. Pestka S, Langer JA, Zoon KC, Samuel CE (1987) Interferons and their actions. Annu Rev Biochem 56: 727–777

    Google Scholar 

  32. Pine R, Decker T, Kessler DS, Levy DE, Darnell Jr JE (1990) Purification and cloning of interferon-stimulated gene factor 2 (ISGF 2): ISGF 2 (IRF-1) can bind to the promoters of both beta interferon- and interferon-stimulated genes but is not a primary transcriptional activator of either. Mol Cell Biol 10: 2448–2457

    Google Scholar 

  33. Porter ACG, Chernajovsky Y, Dale TC, Gilbert CS, Stark GR, Kerr IM (1988) Interferon response element of the human gene 6–16. EMBO J 7: 85–92

    Google Scholar 

  34. Reich N, Evans B, Levy D, Fahey D, Knight Jr E, Darnell Jr JE (1987) Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element. Proc Natl Acad Sci USA 84: 6394–6398

    Google Scholar 

  35. Reid LE, Brasnett AH, Gilbert CS, Porter ACG, Gewert DR, Stark GR, Kerr IM (1989) A single DNA response element can confer inducibility by both alpha- and gamma-interferons. Proc Natl Acad Sci USA 86: 840–844

    Google Scholar 

  36. Revel M, Chebath J (1986) Interferon-activated genes. Trends Biochem Sci 11: 166–170

    Google Scholar 

  37. Rutherford MN, Hannigan GE, Williams BRG (1988) Interferon-induced binding of nuclear factors to promoter elements of the 2–5 A synthetase gene. EMBO J 7: 751–759

    Google Scholar 

  38. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  39. Smale ST, Baltimore D (1989) The “initiator” as a transcription control element. Cell 57: 103–113

    Google Scholar 

  40. Smale ST, Schmidt MC, Berk AJ, Baltimore D (1990) Transcriptional activation by Sp1 as directed through TATA or initiator: specific requirement of mammalian transcription factor IID. Proc Natl Acad Sci USA 87: 4509–4513

    Google Scholar 

  41. Staeheli P, Horisberger MA, Haller O (1984) Mx-dependent resistance to influenza viruses is induced by mouse interferons alpha and beta but not gamma. Virology 132: 456–461

    Google Scholar 

  42. Staeheli P, Danielson P, Haller O, Sutcliffe G (1986) Transcriptional activation of the mouse Mx gene by type 1 interferon. Mol Cell Biol 6: 4770–4774

    Google Scholar 

  43. Staeheli P, Haller O, Boll W, Lindenmann J, Weissmann C (1986) Mx protein: constitutive expression in 3T3 cells transformed with cloned Mx cDNA confers selective resistance to influenza virus. Cell 44: 147–158

    Google Scholar 

  44. Staeheli P, Haller O (1987) Interferon-induced Mx protein: a mediator of cellular resistance to influenza virus. In: Gresser I (ed) Interferon, vol 8. Academic Press, London, pp 1–23

    Google Scholar 

  45. Taylor JL, Grossberg SE (1990) Recent progress in interferon research: molecular mechanisms of regulation, action and virus circumvention. Virus Res 15: 1–25

    Google Scholar 

  46. Wathelet MG, Clauss IM, Content J, Huez GA (1988) Regulation of two interferon-inducible human genes by interferon, poly(rI) · poly(rC) and viruses. Eur J Biochem 174: 323–329

    Google Scholar 

  47. Weitz F, Bekisz J, Zoon K, Arnheiter H (1989) Purification and characterization of a human Mx protein. J Interferon Res 9: 679–689

    Google Scholar 

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Authors and Affiliations

  1. Unit of Veterinary Molecular and Cellular Biology, The Royal Veterinary College, University of London, London, U.K.

    K. C. Chang, E. Hansen, J. Lida & G. Goldspink

  2. Laboratory of Molecular Biology, MRC Centre, Cambridge, U.K.

    Letizia Foroni

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Chang, K.C., Hansen, E., Foroni, L. et al. Molecular and functional analysis of the virus- and interferon-inducible human MxA promoter. Archives of Virology 117, 1–15 (1991). https://doi.org/10.1007/BF01310488

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  • DOI: https://doi.org/10.1007/BF01310488

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