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PMID: 2552141 Published · ppublish English Journal Article

Beta and gamma interferons act synergistically to produce an antiviral state in cells resistant to both interferons individually.

Journal of virology ·Vol. 63 ·No. 11 ·1989-11-00 ·Pages 4569-78

Lewis JA, Huq A, Shan B

Abstract

We showed previously that the mouse fibroblastoid cell line Ltk-aprt- is resistant to the antiviral effects of beta interferon. This lack of response reflects a partial sensitivity to the interferon that is accompanied by a failure to activate expression of several interferon-regulated genes, although certain other genes respond in a normal manner. We show here that Ltk-aprt- cells were also unable to establish an antiviral state and to activate expression of 2,5-oligo(A) synthetase when treated with gamma interferon. Strikingly, however, treatment with a combination of beta interferon and gamma interferon provided complete protection against viral replication. Although the cells were completely insensitive to up to 250 U of the interferons per ml added singly, essentially complete protection from viral cytopathic effects was achieved when as little as 10 U of each of the interferons per ml were combined. Expression of 2,5-oligo(A) synthetase was also sensitive to this synergistic effect. Activation of an antiviral state could also be achieved by sequential treatment, first with gamma interferon and then with beta interferon. Partial protection against viral replication could be achieved by pretreatment with gamma interferon for as little as 1 h before incubation with beta interferon and could be blocked by the addition of specific antibodies or by cycloheximide, indicating that gamma interferon induces the synthesis of a protein which can act synergistically with a signal produced by the beta-interferon receptor. We suggest that Ltk-aprt- cells suffer from defects in one or more components of the gene activation pathways for both type I and type II interferons. Nonetheless, gamma interferon is able to activate the expression of a gene encoding a protein required for signal transduction. This protein acts synergistically with a transient signal produced in response to beta interferon, thereby activating the expression of a further group of genes.

MeSH Terms
2',5'-Oligoadenylate Synthetase/genetics,metabolism Animals Cycloheximide/pharmacology Drug Resistance Drug Synergism Gene Expression/drug effects Gene Expression Regulation/drug effects Interferon Type I/pharmacology Interferon-gamma/pharmacology L Cells/drug effects,metabolism Mice Models, Genetic RNA, Messenger/drug effects,genetics Recombinant Proteins Signal Transduction/drug effects Transcription, Genetic/drug effects Transcriptional Activation Vesicular stomatitis Indiana virus/drug effects,growth & development
Chemicals
Interferon Type I RNA, Messenger Recombinant Proteins Interferon-gamma Cycloheximide 2',5'-Oligoadenylate Synthetase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lewis J A
Department of Anatomy and Cell Biology, SUNY Health Science Center, Brooklyn 11203.
Huq A
Shan B
References (50)
50 references, click to expand
  1. Initial characterization of a spontaneous interferon secreted during growth and differentiation of Friend erythroleukemia cells.
    Mol Cell Biol. 1982 Dec;2(12):1472-80 PMID: 14582189
  2. Functional equivalents of interferon-mediated signals needed for induction of an mRNA can be generated by double-stranded RNA and growth factors.
    EMBO J. 1987 Nov;6(11):3373-8 PMID: 2828026
  3. Evidence that types I and II interferons have different receptors.
    Nature. 1981 Dec 24;294(5843):768-70 PMID: 6172715
  4. Potentiation of the direct anticellular activity of mouse interferons: mutual synergism and interferon concentration dependence.
    Cancer Res. 1982 Mar;42(3):869-75 PMID: 6174218
  5. Effect of primary amines on interferon action.
    Virology. 1982 Mar;117(2):510-5 PMID: 6175094
  6. High-affinity binding of 125I-labeled mouse interferon to a specific cell surface receptor. IV. Mouse gamma interferon and cholera toxin do not compete for the common receptor site of alpha / beta interferon.
    Virology. 1982 Mar;117(2):541-4 PMID: 6175095
  7. Microinjection of interferon and 2',5'-oligoadenylate into mouse L cells and their effects on virus growth.
    J Biochem. 1982 Jun;91(6):2021-8 PMID: 6181054
  8. Specific binding of 125I-human interferon-gamma to high affinity receptors on human fibroblasts.
    J Biol Chem. 1982 Oct 10;257(19):11301-4 PMID: 6288678
  9. Preferential effect of gamma interferon on the synthesis of HLA antigens and their mRNAs in human cells.
    Nature. 1982 Oct 28;299(5886):833-6 PMID: 6290893
  10. Interferon response element of the human gene 6-16.
    EMBO J. 1988 Jan;7(1):85-92 PMID: 3359997
  11. 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
  12. Uptake of extracellular Ca2+ and not recruitment from internal stores is essential for T lymphocyte proliferation.
    Eur J Immunol. 1988 Jun;18(6):917-22 PMID: 3133231
  13. 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
  14. The interaction of interferon-alpha and -gamma: regulation of (2-5)A synthetase activity.
    Virology. 1988 Jul;165(1):87-94 PMID: 2455384
  15. 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
  16. Cell surface receptor-mediated internalization of interferon: its relation to the antiviral activity of interferon.
    J Gen Virol. 1983 Nov;64 (Pt 11):2409-18 PMID: 6196440
  17. Synergistic antiviral and antiproliferative activities of Escherichia coli-derived human alpha, beta, and gamma interferons.
    J Virol. 1984 Feb;49(2):490-6 PMID: 6319748
  18. Mx-dependent resistance to influenza viruses is induced by mouse interferons alpha and beta but not gamma.
    Virology. 1984 Jan 30;132(2):456-61 PMID: 6322423
  19. Induction of an anti-viral response and 2',5'-oligo A synthetase by interferon in several thymidine kinase-deficient cell lines.
    Virology. 1984 Mar;133(2):464-9 PMID: 6324463
  20. Monoclonal antibody to murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activities.
    J Exp Med. 1984 May 1;159(5):1560-5 PMID: 6425450
  21. Receptors for human gamma interferon: binding and crosslinking of 125I-labeled recombinant human gamma interferon to receptors on WISH cells.
    Proc Natl Acad Sci U S A. 1984 Aug;81(16):5160-4 PMID: 6089181
  22. Receptors for human alpha and beta interferon but not for gamma interferon are specified by human chromosome 21.
    Proc Natl Acad Sci U S A. 1984 Sep;81(17):5504-8 PMID: 6206498
  23. Expression of the 2-5A system during the cell cycle.
    Exp Cell Res. 1985 Jul;159(1):27-36 PMID: 4029267
  24. Different mechanisms for activation of gene transcription by interferons alpha and gamma.
    Virology. 1985 Jul 15;144(1):173-80 PMID: 3933177
  25. Abrogation of species specificity for activation of tumoricidal properties in macrophages by recombinant mouse or human interferon-gamma encapsulated in liposomes.
    J Immunol. 1985 Dec;135(6):4289-96 PMID: 3934281
  26. Platelet-derived growth factor and double-stranded ribonucleic acids stimulate expression of the same genes in 3T3 cells.
    Cell. 1985 Dec;43(3 Pt 2):793-800 PMID: 3000615
  27. Differential regulation of interferon-induced mRNAs and c-myc mRNA by alpha- and gamma-interferons.
    Eur J Biochem. 1985 Dec 2;153(2):367-71 PMID: 3935435
  28. Interferon-induced gene expression in wild-type and interferon-resistant human lymphoblastoid (Daudi) cells.
    J Virol. 1986 Jan;57(1):362-6 PMID: 2934555
  29. Binding and cross-linking of recombinant mouse interferon-gamma to receptors in mouse leukemic L1210 cells; interferon-gamma internalization and receptor down-regulation.
    J Immunol. 1986 Apr 1;136(7):2451-5 PMID: 2936825
  30. Expression of extracellular and intracellular human IFN-gamma in mouse L cells transformed with the human IFN-gamma cDNA gene.
    Biochem Biophys Res Commun. 1986 Mar 28;135(3):894-901 PMID: 2421724
  31. 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
  32. Gene induction by interferons and double-stranded RNA: selective inhibition by 2-aminopurine.
    Mol Cell Biol. 1988 Oct;8(10):4289-94 PMID: 2460741
  33. Interferon-induced expression of different genes is mediated by distinct regulatory pathways.
    Virology. 1989 May;170(1):277-81 PMID: 2470194
  34. Transcriptional regulation of interferon-responsive genes is closely linked to interferon receptor occupancy.
    EMBO J. 1986 Jul;5(7):1607-13 PMID: 3017707
  35. Regulation of synthesis and turnover of an interferon-inducible mRNA.
    Mol Cell Biol. 1986 Jun;6(6):2062-7 PMID: 3097508
  36. Interferon and major histocompatibility complex genes: a model to analyse eukaryotic gene regulation?
    Interferon. 1986;7:47-87 PMID: 2434435
  37. Expression of interferon-inducible genes in RD-114 cells.
    J Virol. 1987 May;61(5):1524-31 PMID: 3106649
  38. Interaction of interferon with cellular receptors. Internalization and degradation of cell-bound interferon.
    J Biol Chem. 1982 Nov 25;257(22):13291-6 PMID: 6292184
  39. Interferon receptors. Cross-linking of human leukocyte interferon alpha-2 to its receptor on human cells.
    J Biol Chem. 1982 Dec 10;257(23):13884-7 PMID: 6292213
  40. Synergistic activities of type I (alpha, beta) and type II (gamma) murine interferons.
    Antiviral Res. 1982 Sep;2(4):227-39 PMID: 6293377
  41. A unique set of polypeptides is induced by gamma interferon in addition to those induced in common with alpha and beta interferons.
    Nature. 1983 Feb 3;301(5899):437-9 PMID: 6218412
  42. Induction of an antiviral response by interferon requires thymidine kinase.
    Proc Natl Acad Sci U S A. 1983 Jan;80(1):26-30 PMID: 6185957
  43. Microinjected interferon does not promote an antiviral response in Hela cells.
    Biochem Biophys Res Commun. 1983 Jan 14;110(1):155-60 PMID: 6301439
  44. Interferon induction of fibroblast proteins with guanylate binding activity.
    J Biol Chem. 1983 Jun 25;258(12):7746-50 PMID: 6305951
  45. The mechanism of action of interferon.
    Horiz Biochem Biophys. 1982;6:357-84 PMID: 6194098
  46. Human interferon alpha enters cells by receptor-mediated endocytosis.
    Virology. 1983 Oct 15;130(1):195-203 PMID: 6314645
  47. Activation of metallothionein expression is potentiated by DNA sequences present in the herpes simplex virus thymidine kinase gene.
    FEBS Lett. 1987 Jun 15;217(2):292-6 PMID: 3036584
  48. Differential regulation of a cellular gene by human interferon-gamma and interferon-alpha.
    J Biol Chem. 1988 Jan 5;263(1):332-9 PMID: 3121611
  49. Induction of an antiviral state by interferon in the absence of elevated levels of 2,5-oligo(A) synthetase and eIF-2 kinase.
    Virology. 1988 Jan;162(1):118-27 PMID: 2447700
  50. Potentiation of interferon activity by mixed preparations of fibroblast and immune interferon.
    Infect Immun. 1979 Oct;26(1):248-53 PMID: 227796
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.63.11.4569-4578.1989
Published
1989-11-00
Pages
4569-78
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC251090
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.63.11.4569-4578.1989 PMC Full Text View journal details
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