Abstract
To investigate a possible role of cytokines in parvovirus-mediated suppression of tumorigenesis, we tested in cell culture whether parvoviruses are able to induce interferon (IFN)-β, tumor necrosis factor (TNF)-α or interleukin-6 (IL-6). Infection of rodent or human cells with the parvoviruses minute virus of mice (MVM), H-1 or adeno-associated virus (AAV) types 2 or 5 failed to induce expression of the luciferase or β-galactosidase reporter genes transfected into these cells as constructs containing an IFN-β promoter. Parvoviruses did weakly induce synthesis of TNF-α and of IL-6 in cell culture and could slightly enhance synthesis of these cytokines when induced by other agents. These in vitro data suggest that the rather unspecific tumor-suppressive properties of parvoviruses are unlikely to be attributable to stimulation of the synthesis of IFN, TNF or IL-6.
Similar content being viewed by others
References
Aderka D, Holtmann H, Toker L, Hahn T, Wallach D (1986) Tumor necrosis factor induction by Sendai virus. J Immunol 136:2938–2942
Berent SL, Torczynski RM, Bollon AP (1986) Sendai virus induces high levels of tumor necrosis factor mRNA in human peripheral blood leukocytes. Nucleic Acids Res 14:8997–9015
Berns KI, Bohensky RA (1987) Adeno-associated virus: an update. Adv Virus Res 32:243–306
Beutler B, Cerami A (1989) The biology of cachectin/TNF — a primary mediator of the host response. Annu Rev Immunol 7:625–655
Billiau A, Van Damme J, Ceuppens J, Baroja M (1991) Interleukin-6, an ubiquitous cytokine with paracrine as well as endocrine functions. Colloq INSERM 179:133–142
Brandenburger A, Legendre D, Avalosse B, Rommelaere J (1990) NS-1 and NS-2 proteins may act synergistically in the cytopathogenicity of parvovirus MVMp. Virology 174:576–584
Brasier AR, Tate JE, Habener JF (1989) Optimized use of the firefly luciferase assay as a reporter gene in mammalian cell lines. Bio Techniques 7:1116–1122
Caillet Fauquet P, Perros M, Brandenburger A, Spegelaere P, Rommelaere J (1990) Programmed killing of human cells by means of inducible clone of parvoviral genes endocing non-structural proteins. EMBO J 9:2989–2995
Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) An endotoxin — induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72:3666–3670
Chen C, Okayama H (1987) High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 7:2745–2752
Chen L, Mory Y, Zilberstein A, Revel M (1988) Growth inhibition of human breast carcinoma and leukemia/lymphoma cell lines by recombinant inteferon-beta-2. Proc Natl Acad Sci USA 85:8037–8041
Chen YQ, de Foresta F, Hertoghs J, Avalosse BL, Cornelis JJ, Rommelaere J (1986) Selective killing of simian virus 40-transformed human fibroblasts by parvovirus H-1. Cancer Res 46:3574–3579
Clemens MJ, McNurlan MA (1985) Regulation of cell proliferation and differentiation by interferons. Biochem J 226:345–360
Cornelis JJ, Avalosse BL, Mousset S, Namba M, Rommelaere J (1986) Selective destruction by parvoviruses of human and mouse fibroblasts transformed with γ iradiation. Int J Radiat Biol 49:529
Cornelis JJ, Becquart P, Duponchel N, Salomé N, Avalosse BL, Namba M, Rollelaere J (1988a) Transformation of human fibroblasts by ionizing radiation, a chemical carcinogen, or simian virus 40 correlates with an increase in susceptibility to the autonomous parvovirus H-1 virus and minute virus of mice. J Virol 62:1679–1686
Cornelis JJ, Spruyt N, Spegelaere P, Guetta E, Darawshi T, Cotmore SF, Tal J, Rommelaere J (1988b) Sensitization of transformed rat fibroblasts to killing by parvovirus minute virus of mice correlates with an increase in viral gene expression. J Virol 62:3438–3444
Cukor G, Blacklow NR, Hoggan D, Berns KI (1984) Biology of adeno-associated virus. In: Berns KI (ed) The parvoviruses. Plenum Press, New York, pp 33–66
Darrigrand AA, Singh SB, Lang CM (1984) Effects of Kilham rat virus on natural killer cellmediated cytotoxicity in brown Norway and Wistar Furth rats. Am J Vet Res 45:200–202
De la Maza LM, Carter BJ (1981) Inhibition of adenovirus oncogenicity in hamsters by adenoassociated virus DNA. J Natl Cancer Inst 67:1323–1326
Dinter H, Hauser H (1987) Cooperative interaction of multiple DNA elements in the human interferon-β promoter. Eur J Biochem 166:103–109
Engers HD, Louis JA, Zubler RH, Hirt B (1981) Inhibition of T cell-mediated functions by MVM (i), a parvovirus closely related to minute virus of mice. J Immunol 127:2280–2285
Faisst S, Schlehofer JR, zur Hausen H (1989) Transformation of human cells by oncogenic viruses supports permissiveness for parvovirus H-1 propagation. J Virol 63:2152–2158
Fujita A, Ohno S, Yasumitsu H, Taniguchi T (1985) Delimitation and properties of DNA sequences required for the regulated expression of human interferon β-gene. Cell 41:489–496
Goodburn S, Zinn K, Maniatis T (1985) Human β-interferon gene expression is regulated by an inducible enhancer element. Cell 41:509–520
Goodburn S, Burnstein H, Maniatis T (1986) The human interferon gene enhancer is under negative control. Cell 45:601–610
Guetta E, Mincberg M, Mousset S, Bertinchamps C, Rommelaere J, Tal J (1990) Selective killing of transformed rat cells by minute virus of mice does not require infectious virus production. J Virol 64:458–462
Harris RE, Coleman PH, Morahan PS (1974) Erythrocyte association and interferon production by minute virus of mice. Proc Soc Exp Biol Med 145:1288–1292
Heilbronn R, Schlehofer JR, zur Hausen H (1984) Selective killing of carcinogen — treated SV40-transformed Chinese hamster cells by a defective parvovirus. Virology 136:439–441
Heilbronn R, Schlehofer JR, Yalkinoglu AÖ, zur Hausen H (1985) Selective DNA amplification induced by carcinogens (initiators): evidence for a role of proteases and DNA polymerase α. Int J Cancer 36:85–91
Jacobsen H, Mestan J, Mittnacht S, Dieffenbach CW (1989) Beta interferon subtype 1 induction by tumor necrosis factor. Mol Cell Biol 9:3037–3042
Keller GA, Gould S, DeLuca M, Subramani S (1987) Firefly luciferase is targeted to peroxisomes in mammalian cells. Proc Natl Acad Sci USA 84:3264–3268
Kilham L, Buckler CE, Ferm VH, Baron S (1968) Production of interferon during rat virus infection. Proc Soc Exp Biol Med 129:274–278
Klein-Bauernschmitt P, zur Hausen H, Schlehofer JR (1992) Induction of differentiation associated changes in established human cells by infection with adeno-associated virus type 2. J Virol 66:4191–4200
Kohase M, Henriksen-De Stefano D, May LT, Vilcek J, Sehgal PB (1986) Induction of β-2, interferon by TNF: a homeostatic mechanism in the control of cell proliferation. Cell 45:659–666
Le J, Vilcek J (1989) Interleukin 6: a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab Invest 61:588–602
Loetscher H, Steinmetz M, Lesslauer W (1991) Tumor necrosis factor: receptors and inhibitors. Cancer cells 3:221–226
Lorence RM, Rood PA, Kelley KW (1988) Newcastle disease virus as antineoplastic agent: induction of tumor necrosis factor — alpha and augmentation of its cytotoxicity. J Natl Cancer Inst 80:1305–1312
Maroteaux L, Kakana C, Mory Y, Groner Y, Revel M (1983) Sequences involved in the regulated expression of the human interferon-β1 gene in recombinant SV40 DNA vectors replicating in monkey cells. EMBO J 2:325–332
Mousset S, Rommelaere J (1982) Minute virus of mice inhibits cell transformation by simian virus 40. Nature 300:537–539
Mousset S, Cornelis J, Spruyt N, Rommelaere J (1986) Transformation of established murine fibroblasts with activated cellular Harvey — ras oncogene or the polyoma virus middle T gene increases cell permissiveness to parvovirus minute virus of mice. Biochimie 68:951–955
Männel DN, Falk W (1989) Optimal induction of tumor necrosis factor production in human monocytes requires complete S-form lipopolysaccharide. Infect Immun 57:1953–1958
Ohno S, Taniguchi T (1983) The 5′-flanking sequence of human interferon-β1 genes is responsible for viral induction of transcription. Nucleic Acids Res 11:5403–5412
Oie HK, Gazdar AF, Buckler CE, Baron S (1972) High interferon producing line of transformed murine cells. J Gen Virol 17:107–109
Old LJ (1985) Tumor necrosis factor (TNF). Science 230:630–632
Ray A, Tatter SB, May LT, Sehgal PB (1988) Activation of the human “β-2-interferon/hepatocyte-stimulating factor/interleukin 6” promoter by cytokines, viruses, and second messenger agonists. Proc Natl Acad Sci USA 85:7601–6705
Rommelaere J (1990) Action anticancéreuse des parvovirus médecine/science 6:534–543
Rommelaere J, Cornelis JJ (1991) Antineoplastic activity of parvoviruses. J Virol Methods 33:233–251
Rommelaere J, Tattersall P (1990) Oncosuppression by parvoviruses In: Tijssen P (ed) Handbook of parvoviruses, vol II. CRC Press, Boca Raton, pp 41–57
Salomé N, van Hille B, Duponchel N, et al. (1990) Sensitization of transformed rat cells to parvovirus MVMp is restricted to specific oncogenes. Oncogene 5:123–130
Schlehofer JR, Heilbronn R, Georg-Fries B, zur Hausen H (1983) Inhibition of initiator — induced SV40 gene amplification in SV40-transformed Chinese hamster cells by infection with a defective parvovirus. Int J Cancer 32:591–595
Schlehofer JR, Ehrbar M, zur Hausen H (1986) Vaccinia virus, herpes simplex virus and carcinogens induce DNA amplification in a human cell line and support replication of a helper virus dependent parvovirus. Virology 152:110–117
Schlehofer JR, Heilbronn R (1990) Infection with adeno-associated virus type 5 inhibits mutagenicity of herpes simplex virus type 1 or 4-nitroquinoline-1-oxide. Mutation Res 244:317–320
Schmitt J, Schlehofer JR, Mergener K, Gissmann L, zur Hausen H (1989) Amplification of bovine papillomavirus DNA by N-methyl-N′-nitro-N′-nitrosoguanidine, ultraviolet irradiation or infection with herpes simplex virus. Virology 171:73–81
Sehgal PB, Grieninger G, Tosato G (eds) (1989) Regulation of the acute phase and immune responses: interleukin-6. Ann New York Acad Sci 557: 1–583
Siegl G, Bates RC, Berns KI, Carter BJ, Kelly DC, Kurstak E, Tattersall P (1985) Characteristics and taxonomy of parvoviridae. Intervirology 23:61–73
Southern PJ, Berg G (1982) Transformation of mammalian cells to antibiotic resistance with a bacterial gene under the control of the SV40 early promoter. J Mol Appl Genet 1:327–341
Thompson JF, Hayes LS, Lloyd DB (1991) Modulation of firefly luciferase stability and impact on studies of gene regulation. Gene 103:171–177
Toolan H, Rhode SL, Gierthy JF (1982) Inhibition of 7,12-dimethylbenz(a)anthraceneinduced tumors in Syrian hamsters by prior infection with H-1 parvovirus. Cancer Res 42:2552–2555
Vara J, Malpartida F, Hopwood DA, Jiménez A (1985) Cloning and expression of a puromycin N′-acetyl-transferase gene from Streptomyces alboniger in Streptomyces lividans and Escherichia coli. Gene 33:197–206
Vara J, Portela A, Ortin J, Jiménez A (1986) Expression in mammalian cells of a gene from Streptomyces alboniger conferring puromycin resistance. Nucleic Acids Res 14:4617–4624
Wiedbrauk DL, Bloom ME, Lodmell DL (1986) Mink parvoviruses and interferons: in vitro studies. J Virol 60:1179–1182
Wiedbrauk DL, Hadlow WJ, Ewalt LC, Lodmell DL (1986) Interferon response in normal and Aleutian disease virus-infected mink. J Virol 59:514–517
Winocour E, Callaham MF, Huberman E (1988) Perturbation of the cell cycle by adeno associated virus. Virology 167:393–399
Yakobson B, Koch T, Winocour E (1987) Replication of adeno-associated virus in synchronized cells without the addition of a helper virus. J Virol 61:972–981
Yalkinoglu AÖ, Heilbronn R, Bürkle A, Schlehofer JR, zur Hausen H (1988) DNA amplification of adeno-associated virus as a response to cellular genotoxic stress. Cancer Res 48:3123–3129
Zinn K, DiMaio D, Maniatis T (1983) Identification of two distinct regulatory regions adjacent to the human interferon gene. Cell 34:865–879
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schlehofer, J.R., Rentrop, M. & Männel, D.N. Parvoviruses are inefficient in inducing interferon-β, tumor necrosis factor-α, or interleukin-6 in mammalian cells. Med Microbiol Immunol 181, 153–164 (1992). https://doi.org/10.1007/BF00202055
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00202055