Home LiteratureArticle Details
PMID: 1376370 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Constitutive expression of an ISGF2/IRF1 transgene leads to interferon-independent activation of interferon-inducible genes and resistance to virus infection.

Journal of virology ·Vol. 66 ·No. 7 ·1992-07-00 ·Pages 4470-8

Pine R

Abstract

Interferon (IFN)-stimulated gene factor 2 (ISGF2) plays a role in transcription of the beta IFN (IFN-beta) gene and IFN-stimulated genes (ISGs) and may function as a central mediator of cytokine responses. Constitutive ISGF2 transgene expression resulted in substantial resistance to three RNA virus families. This phenotype was not a consequence of IFN production and may have arisen directly through ISG expression. ISGF2 acted generally as a positive transcription factor through binding sites from several genes, in the context of transient cotransfection. Constitutive transcription of the endogenous IFN-beta gene, and several genes that are normally induced by either IFN-alpha or IFN-gamma, or only by IFN-alpha, was elevated in cells that constitutively express an ISGF2 transgene. However, constitutive and virus-induced levels of IFN-beta mRNA were unaffected in such cell lines.

MeSH Terms
Antibodies, Viral/immunology Base Sequence DNA, Viral DNA-Binding Proteins/genetics,physiology Gene Expression Regulation HeLa Cells Humans Immunity, Innate/genetics Interferon Regulatory Factor-1 Interferons/genetics,metabolism Molecular Sequence Data Neutralization Tests Phosphoproteins/genetics,physiology Transcription Factors/genetics,physiology Transfection Virus Diseases/immunology Virus Replication
Chemicals
Antibodies, Viral DNA, Viral DNA-Binding Proteins IRF1 protein, human Interferon Regulatory Factor-1 Phosphoproteins Transcription Factors Interferons
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Pine R
Laboratory of Molecular Cell Biology, Rockefeller University, New York, New York 10021-6399.
References (62)
62 references, click to expand
  1. Critical role of a common transcription factor, IRF-1, in the regulation of IFN-beta and IFN-inducible genes.
    EMBO J. 1992 Jan;11(1):185-93 PMID: 1371248
  2. Involvement of a cis-element that binds an H2TF-1/NF kappa B like factor(s) in the virus-induced interferon-beta gene expression.
    Nucleic Acids Res. 1989 May 11;17(9):3335-46 PMID: 2566973
  3. Organization of the murine and human interleukin-7 receptor genes: two mRNAs generated by differential splicing and presence of a type I-interferon-inducible promoter.
    Mol Cell Biol. 1991 Jun;11(6):3052-9 PMID: 2038316
  4. Resistance to influenza virus and vesicular stomatitis virus conferred by expression of human MxA protein.
    J Virol. 1990 Jul;64(7):3370-5 PMID: 2161946
  5. Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated.
    Cell. 1990 Oct 19;63(2):303-12 PMID: 2208287
  6. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators.
    Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670-4 PMID: 2419912
  7. Transcription of interferon-stimulated genes is induced by adenovirus particles but is suppressed by E1A gene products.
    J Virol. 1988 Jan;62(1):114-9 PMID: 2446013
  8. Enhancer-like interferon responsive sequences of the human and murine (2'-5') oligoadenylate synthetase gene promoters.
    EMBO J. 1988 May;7(5):1411-9 PMID: 2457496
  9. Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes.
    Cell. 1989 Aug 25;58(4):729-39 PMID: 2475256
  10. A single DNA response element can confer inducibility by both alpha- and gamma-interferons.
    Proc Natl Acad Sci U S A. 1989 Feb;86(3):840-4 PMID: 2492664
  11. Induction of human interferon gene expression is associated with a nuclear factor that interacts with the NF-kappa B site of the human immunodeficiency virus enhancer.
    J Virol. 1989 Jun;63(6):2557-66 PMID: 2542571
  12. Induction of the transcription factor IRF-1 and interferon-beta mRNAs by cytokines and activators of second-messenger pathways.
    Proc Natl Acad Sci U S A. 1989 Dec;86(24):9936-40 PMID: 2557635
  13. Cytoplasmic activation of ISGF3, the positive regulator of interferon-alpha-stimulated transcription, reconstituted in vitro.
    Genes Dev. 1989 Sep;3(9):1362-71 PMID: 2606351
  14. Constitutive expression of (2'-5') oligo A synthetase confers resistance to picornavirus infection.
    Nature. 1987 Dec 10-16;330(6148):587-8 PMID: 2825034
  15. Molecular cloning and expression of the human interferon-gamma receptor.
    Cell. 1988 Oct 21;55(2):273-80 PMID: 2971451
  16. Cloning and complete sequence of an HLA-A2 gene: analysis of two HLA-A alleles at the nucleotide level.
    J Immunol. 1985 Apr;134(4):2727-33 PMID: 2982951
  17. Mx protein: constitutive expression in 3T3 cells transformed with cloned Mx cDNA confers selective resistance to influenza virus.
    Cell. 1986 Jan 17;44(1):147-58 PMID: 3000619
  18. Nonidentical induction of the guanylate binding protein and the 56K protein by type I and type II interferons.
    J Interferon Res. 1986 Aug;6(4):417-27 PMID: 3095442
  19. Interferon response element of the human gene 6-16.
    EMBO J. 1988 Jan;7(1):85-92 PMID: 3359997
  20. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements.
    Cell. 1988 Sep 9;54(6):903-13 PMID: 3409321
  21. Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element.
    Proc Natl Acad Sci U S A. 1987 Sep;84(18):6394-8 PMID: 3476954
  22. Increased rate of degradation of c-myc mRNA in interferon-treated Daudi cells.
    Proc Natl Acad Sci U S A. 1985 Aug;82(15):4896-9 PMID: 3860831
  23. Analysis of interferon mRNA in human fibroblast cells induced to produce interferon.
    Proc Natl Acad Sci U S A. 1981 Dec;78(12):7426-30 PMID: 6174973
  24. Transcriptional induction of two genes in human cells by beta interferon.
    Proc Natl Acad Sci U S A. 1984 Nov;81(21):6733-7 PMID: 6436820
  25. Double-stranded RNA activates binding of NF-kappa B to an inducible element in the human beta-interferon promoter.
    EMBO J. 1989 Apr;8(4):1129-38 PMID: 2663471
  26. In vivo evidence of interaction between interferon-stimulated gene factors and the interferon-stimulated response element.
    Mol Cell Biol. 1989 Aug;9(8):3533-7 PMID: 2796995
  27. Evidence for a nuclear factor(s), IRF-1, mediating induction and silencing properties to human IFN-beta gene regulatory elements.
    EMBO J. 1988 Nov;7(11):3397-405 PMID: 2850164
  28. Cells resistant to interferon are defective in activation of a promoter-binding factor.
    EMBO J. 1988 Dec 1;7(12):3779-83 PMID: 2974800
  29. Organization of the murine Mx gene and characterization of its interferon- and virus-inducible promoter.
    Mol Cell Biol. 1988 Aug;8(8):3065-79 PMID: 2974922
  30. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat.
    Cell. 1985 Jul;41(3):813-23 PMID: 2988790
  31. Protein kinase C phosphorylation at Thr 654 of the unoccupied EGF receptor and EGF binding regulate functional receptor loss by independent mechanisms.
    Cell. 1986 Mar 28;44(6):839-48 PMID: 3006920
  32. Transcriptional stimulation by CaPO4-DNA precipitates.
    Nucleic Acids Res. 1988 Feb 25;16(4):1371-8 PMID: 3126485
  33. Transcriptional activation of HLA-DR alpha by interferon gamma requires a trans-acting protein.
    Proc Natl Acad Sci U S A. 1988 Jul;85(13):4672-6 PMID: 3133656
  34. Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control.
    Genes Dev. 1988 Apr;2(4):383-93 PMID: 3371658
  35. Antiviral state against influenza virus neutralized by microinjection of antibodies to interferon-induced Mx proteins.
    EMBO J. 1988 May;7(5):1315-20 PMID: 3409866
  36. Interferon-stimulated transcription: isolation of an inducible gene and identification of its regulatory region.
    Proc Natl Acad Sci U S A. 1986 Dec;83(23):8929-33 PMID: 3466167
  37. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation.
    Cell. 1986 Aug 29;46(5):659-67 PMID: 3488815
  38. alpha-Interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences.
    Nature. 1985 Apr 18-24;314(6012):637-9 PMID: 3990797
  39. High efficiency DNA-mediated transformation of primate cells.
    Science. 1983 Aug 5;221(4610):551-3 PMID: 6306768
  40. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  41. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells.
    Cell. 1984 Oct;38(3):745-55 PMID: 6548414
  42. Evidence that a human beta-tubulin pseudogene is derived from its corresponding mRNA.
    Nature. 1982 May 6;297(5861):83-4 PMID: 7070533
  43. Human metallothionein genes--primary structure of the metallothionein-II gene and a related processed gene.
    Nature. 1982 Oct 28;299(5886):797-802 PMID: 7133118
  44. Two levels of regulation of beta-interferon gene expression in human cells.
    Proc Natl Acad Sci U S A. 1983 Jul;80(13):3923-7 PMID: 6575385
  45. Induced expression of the endogenous beta interferon gene in adenovirus type 5-transformed rat fibroblasts.
    J Virol. 1992 Apr;66(4):1884-90 PMID: 1548745
  46. Interferon induction of gene transcription analyzed by in vivo footprinting.
    Mol Cell Biol. 1992 Jan;12(1):1-9 PMID: 1729591
  47. Activation of IFN-beta element by IRF-1 requires a posttranslational event in addition to IRF-1 synthesis.
    Nucleic Acids Res. 1991 Aug 25;19(16):4421-8 PMID: 1886766
  48. Cytoplasmic activation of GAF, an IFN-gamma-regulated DNA-binding factor.
    EMBO J. 1991 Apr;10(4):927-32 PMID: 1901265
  49. Synergistic interaction between interferon-alpha and interferon-gamma through induced synthesis of one subunit of the transcription factor ISGF3.
    EMBO J. 1990 Apr;9(4):1105-11 PMID: 2108862
  50. Genetic transfer of a functional human interferon alpha receptor into mouse cells: cloning and expression of its cDNA.
    Cell. 1990 Jan 26;60(2):225-34 PMID: 2153461
  51. Activity of rat Mx proteins against a rhabdovirus.
    J Virol. 1990 Dec;64(12):6263-9 PMID: 2173790
  52. ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8555-9 PMID: 2236065
  53. Purification and cloning of interferon-stimulated gene factor 2 (ISGF2): ISGF2 (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. 1990 Jun;10(6):2448-57 PMID: 2342456
  54. Interferons and their actions.
    Annu Rev Biochem. 1987;56:727-77 PMID: 2441659
  55. Interferon-induced binding of nuclear factors to promoter elements of the 2-5A synthetase gene.
    EMBO J. 1988 Mar;7(3):751-9 PMID: 2456211
  56. Two interferon-induced nuclear factors bind a single promoter element in interferon-stimulated genes.
    Proc Natl Acad Sci U S A. 1988 Nov;85(22):8521-5 PMID: 2460869
  57. Interferon receptors.
    Immunol Today. 1988 Dec;9(12):393-400 PMID: 2475121
  58. Constitutive expression of a 2',5'-oligoadenylate synthetase cDNA results in increased antiviral activity and growth suppression.
    J Interferon Res. 1989 Dec;9(6):649-57 PMID: 2481699
  59. The involvement of NF-kappa B in beta-interferon gene regulation reveals its role as widely inducible mediator of signal transduction.
    Cell. 1989 Apr 21;57(2):287-94 PMID: 2495183
  60. Interactions of alpha- and gamma-interferon in the transcriptional regulation of the gene encoding a guanylate-binding protein.
    EMBO J. 1989 Jul;8(7):2009-14 PMID: 2507314
  61. Alpha interferon and gamma interferon stimulate transcription of a single gene through different signal transduction pathways.
    Mol Cell Biol. 1989 Dec;9(12):5404-11 PMID: 2555698
  62. Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons.
    Mol Cell Biol. 1991 Jan;11(1):182-91 PMID: 1898761
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1992-07-00
Pages
4470-8
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC241256
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]