1887

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Volume 88, Issue 3

Thioaptamer decoy targeting of AP-1 proteins influences cytokine expression and the outcome of arenavirus infections Free

Abstract

Viral haemorrhagic fever (VHF) is caused by a number of viruses, including arenaviruses. The pathogenesis is believed to involve dysregulation of cytokine production. The arenaviruses and have a tropism for macrophages and other reticuloendothelial cells and both appear to suppress the normal macrophage response to virus infection. A decoy thioaptamer, XBY-S2, was developed and was found to bind to AP-1 transcription factor proteins. The P388D1 macrophage-like cell line contains members of the AP-1 family which may act as negative regulators of AP-1-controlled transcription. XBY-S2 was found to bind to Fra-2 and JunB, and enhance the induction of cytokines IL-6, IL-8 and TNF-, while reducing the binding to AP-1 promoter elements. Administration of XBY-S2 to Pichinde virus-infected guinea pigs resulted in a significant reduction in Pichinde virus-induced mortality and enhanced the expression of cytokines from primary guinea pig macrophages, which may contribute to its ability to increase survival of Pichinde virus-infected guinea pigs. These data demonstrate a proof of concept that thioaptamers can be used to modulate the outcome of viral infections by arenaviruses by the manipulation of transcription factors involved in the regulation of the immune response.

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2007-03-01
2024-04-19
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References

  1. Adcock I. M. 1997; Transcription factors as activators of gene transcription: AP-1 and NF-kappa B. Monaldi Arch Chest Dis 52:178–186
     [Google Scholar]
  2. Alexopoulou L., Holt A. C., Medzhitov R., Flavell R. A. 2001; Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732–738 [CrossRef]
     [Google Scholar]
  3. Aronson J. F., Herzog N. K., Jerrells T. R. 1994; Pathological and virological features of arenavirus disease in guinea pigs. Comparison of two Pichinde virus strains. Am J Pathol 145:228–235
     [Google Scholar]
  4. Aronson J. F., Herzog N. K., Jerrells T. R. 1995; Tumor necrosis factor and the pathogenesis of Pichinde virus infection in guinea pigs. Am J Trop Med Hyg 52:262–269
     [Google Scholar]
  5. Baize S., Leroy E. M., Georges-Courbot M. C., Capron M., Lansoud-Soukate J., Debre P., Fisher-Hoch S. P., McCormick J. B., Georges A. J. 1999; Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nat Med 5:423–426 [CrossRef]
     [Google Scholar]
  6. Baize S., Kaplon J., Faure C., Pannetier D., Georges-Courbot M. C., Deubel V. 2004; Lassa virus infection of human dendritic cells and macrophages is productive but fails to activate cells. J Immunol 172:2861–2869 [CrossRef]
     [Google Scholar]
  7. Bielinska A., Shivdasani R. A., Zhang L. Q., Nabel G. J. 1990; Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. Science 250:997–1000 [CrossRef]
     [Google Scholar]
  8. Casola A., Garofalo R. P., Jamaluddin M., Vlahopoulos S., Brasier A. R. 2000; Requirement of a novel upstream response element in respiratory syncytial virus-induced IL-8 gene expression. J Immunol 164:5944–5951 [CrossRef]
     [Google Scholar]
  9. Chinenov Y., Kerppola T. K. 2001; Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity. Oncogene 20:2438–2452 [CrossRef]
     [Google Scholar]
  10. Cho-Chung Y. S., Park Y. G., Lee Y. N. 1999; Oligonucleotides as transcription factor decoys. Curr Opin Mol Ther 1:386–392
     [Google Scholar]
  11. De Cesare D., Fimia G. M., Sassone-Corsi P. 1999; Signaling routes to CREM and CREB: plasticity in transcriptional activation. Trends Biochem Sci 24:281–285 [CrossRef]
     [Google Scholar]
  12. Du W., Thanos D., Maniatis T. 1993; Mechanisms of transcriptional synergism between distinct virus-inducible enhancer elements. Cell 74:887–898 [CrossRef]
     [Google Scholar]
  13. Dyer R. B., Herzog N. K. 1995; Isolation of intact nuclei for nuclear extract preparation from fragile B-lymphocyte cell lines. Biotechniques 19:192–195
     [Google Scholar]
  14. Dyer R. B., Collaco C., Niesel D. W., Herzog N. K. 1993; Shigella flexneri invasion of HeLa cells induces κ B DNA-binding activity. Infect Immun 61:4427–4433
     [Google Scholar]
  15. Eleouet J. F., Chilmonczyk S., Besnardeau L., Laude H. 1998; Transmissible gastroenteritis coronavirus induces programmed cell death in infected cells through a caspase-dependent pathway. J Virol 72:4918–4924
     [Google Scholar]
  16. Falvo J. V., Uglialoro A. M., Brinkman B. M., Merika M., Parekh B. S., Tsai E. Y., King H. C., Morielli A. D., Peralta E. G. other authors 2000; Stimulus-specific assembly of enhancer complexes on the tumor necrosis factor alpha gene promoter. Mol Cell Biol 20:2239–2247 [CrossRef]
     [Google Scholar]
  17. Fennewald S. M., Aronson J. F., Zhang L., Herzog N. K. 2002; Alterations in NF-kappaB and RBP-Jkappa by arenavirus infection of macrophages in vitro and in vivo. J Virol 76:1154–1162 [CrossRef]
     [Google Scholar]
  18. Fisher-Hoch S., McCormick J. B., Sasso D., Craven R. B. 1988; Hematologic dysfunction in Lassa fever. J Med Virol 26:127–135 [CrossRef]
     [Google Scholar]
  19. Flick D. A., Gifford G. E. 1984; Comparison of in vitro cell cytotoxic assays for tumor necrosis factor. J Immunol Methods 68:167–175 [CrossRef]
     [Google Scholar]
  20. Giese K., Kingsley C., Kirshner J. R., Grosschedl R. 1995; Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1-induced DNA bending and multiple protein-protein interactions. Genes Dev 9:995–1008 [CrossRef]
     [Google Scholar]
  21. Hoffmann E., Dittrich-Breiholz O., Holtmann H., Kracht M. 2002; Multiple control of interleukin-8 gene expression. J Leukoc Biol 72:847–855
     [Google Scholar]
  22. Jin G., Howe P. H. 1997; Regulation of clusterin gene expression by transforming growth factor beta. J Biol Chem 272:26620–26626 [CrossRef]
     [Google Scholar]
  23. Karin M., Shaulian E. 2001; AP-1: linking hydrogen peroxide and oxidative stress to the control of cell proliferation and death. IUBMB Life 52:17–24 [CrossRef]
     [Google Scholar]
  24. King D. J., Bassett S. E., Li X., Fennewald S. M., Herzog N. K., Luxon B. A., Shope R., Gorenstein D. G. 2002; Combinatorial selection and binding of phosphorothioate aptamers targeting human NF-kappa B RelA(p65) and p50. Biochemistry 41:9696–9706 [CrossRef]
     [Google Scholar]
  25. Komastu T., Ireland D. D., Reiss C. S. 1998; IL-12 and viral infections. Cytokine Growth Factor Rev 9:277–285 [CrossRef]
     [Google Scholar]
  26. Kuo H. P., Hwang K. H., Lin H. C., Lu L. C. 1997; Effect of endogenous nitric oxide on tumour necrosis factor-alpha-induced leukosequestration and IL-8 release in guinea-pigs airways in vivo. Br J Pharmacol 122:103–111 [CrossRef]
     [Google Scholar]
  27. Leroy E. M., Baize S., Volchkov V. E., Fisher-Hoch S. P., Georges-Courbot M. C., Lansoud-Soukate J., Capron M., Debre P., McCormick J. B., Georges A. J. 2000; Human asymptomatic Ebola infection and strong inflammatory response. Lancet 355:2210–2215 [CrossRef]
     [Google Scholar]
  28. Mann M. J. 1998; E2F decoy oligonucleotide for genetic engineering of vascular bypass grafts. Antisense Nucleic Acid Drug Dev 8:171–176 [CrossRef]
     [Google Scholar]
  29. Marshall W. S., Caruthers M. H. 1993; Phosphorodithioate DNA as a potential therapeutic drug. Science 259:1564–1570 [CrossRef]
     [Google Scholar]
  30. Merika M., Williams A. J., Chen G., Collins T., Thanos D. 1998; Recruitment of CBP/p300 by the IFN beta enhanceosome is required for synergistic activation of transcription. Mol Cell 1:277–287 [CrossRef]
     [Google Scholar]
  31. Morishita R., Gibbons G. H., Horiuchi M., Ellison K. E., Nakama M., Zhang L., Kaneda Y., Ogihara T., Dzau V. J. 1995; A gene therapy strategy using a transcription factor decoy of the E2F binding site inhibits smooth muscle proliferation in vivo. Proc Natl Acad Sci U S A 92:5855–5859 [CrossRef]
     [Google Scholar]
  32. Morishita R., Higaki J., Tomita N., Ogihara T. 1998; Application of transcription factor ‘decoy’ strategy as means of gene therapy and study of gene expression in cardiovascular disease. Circ Res 82:1023–1028 [CrossRef]
     [Google Scholar]
  33. Newman J. R. S., Keating A. E. 2003; Comprehensive identification of human bZIP interactions with coiled-coil arrays. Science 300: 2097 [CrossRef]
     [Google Scholar]
  34. Ono S., Date I., Onoda K., Shiota T., Ohmoto T., Ninomiya Y., Asari S., Morishita R. 1998; Decoy administration of NF- κ B into the subarachnoid space for cerebral angiopathy. Hum Gene Ther 9:1003–1011 [CrossRef]
     [Google Scholar]
  35. Orange J. S., Salazar-Mather T. P., Opal S. M., Spencer R. L., Miller A. H., McEwen B. S., Biron C. A. 1995; Mechanism of interleukin-12-mediated toxicities during experimental viral infections: role of tumor necrosis factor and glucocorticoids. J Exp Med 181:901–914 [CrossRef]
     [Google Scholar]
  36. Osborne S. E., Matsumura I., Ellington A. D. 1997; Aptamers as therapeutic and diagnostic reagents: problems and prospects. Curr Opin Chem Biol 1:5–9 (Review) (34 refs [CrossRef]
     [Google Scholar]
  37. Oswald I. P., Wynn T. A., Sher A., James S. L. 1992; Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor α required as a costimulatory factor for interferon γ -induced activation. Proc Natl Acad Sci U S A 89:8676–8681 [CrossRef]
     [Google Scholar]
  38. Park Y. G., Nesterova M., Agrawal S., Cho-Chung Y. S. 1999; Dual blockade of cyclic AMP response element- (CRE) and AP-1-directed transcription by CRE-transcription factor decoy oligonucleotide. Gene-specific inhibition of tumor growth. J Biol Chem 274:1573–1580 [CrossRef]
     [Google Scholar]
  39. Peters C. J., Jahrling P. B., Liu C. T., Kenyon R. H., McKee K. T. Jr, Barrera-Oro J. G. 1987; Experimental studies of arenavirus hemorrhagic fevers. Curr Top Microbiol Immunol 134:5–68
     [Google Scholar]
  40. Peters C. J., Liu C. T., Anderson G. W. Jr, Morrill J. C., Jahrling P. B. 1989; Pathogenesis of viral hemorrhagic fevers: Rift Valley fever and Lassa fever contrasted. Rev Infect Dis 11 (Suppl. 4):S743–S749 [CrossRef]
     [Google Scholar]
  41. Roy S., Charboneau R., Cain K., DeTurris S., Melnyk D., Barke R. A. 1999; Deficiency of the transcription factor c-Fos increases lipopolysaccharide-induced macrophage interleukin 12 production. Surgery 126:239–247 [CrossRef]
     [Google Scholar]
  42. Rutberg S. E., Saez E., Lo S., Jang S. I., Markova N., Spiegelman B. M., Yuspa S. H. 1997; Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters. Oncogene 15:1337–1346 [CrossRef]
     [Google Scholar]
  43. Shaulian E., Karin M. 2001; AP-1 in cell proliferation and survival. Oncogene 20:2390–2400 [CrossRef]
     [Google Scholar]
  44. Shaulian E., Karin M. 2002; AP-1 as a regulator of cell life and death. Nat Cell Biol 4:E131–E136 [CrossRef]
     [Google Scholar]
  45. Sonobe M. H., Yoshida T., Murakami M., Kameda T., Iba H. 1995; fra-2 promoter can respond to serum-stimulation through AP-1 complexes. Oncogene 10:689–696
     [Google Scholar]
  46. Suzuki T., Okuno H., Yoshida T., Endo T., Nishina H., Iba H. 1991; Difference in transcriptional regulatory function between c-Fos and Fra-2. Nucleic Acids Res 19:5537–5542 [CrossRef]
     [Google Scholar]
  47. Thanos D., Maniatis T. 1995; Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell 83:1091–1100 [CrossRef]
     [Google Scholar]
  48. Tomita S., Tomita N., Yamada T., Zhang L., Kaneda Y., Morishita R., Ogihara T., Dzau V. J., Horiuchi M. 1999; Transcription factor decoy to study the molecular mechanism of negative regulation of renin gene expression in the liver in vivo. Circ Res 84:1059–1066 [CrossRef]
     [Google Scholar]
  49. Tsai E. Y., Falvo J. V., Tsytsykova A. V., Barczak A. K., Reimold A. M., Glimcher L. H., Fenton M. J., Gordon D. C., Dunn I. F., Goldfeld A. E. 2000; A lipopolysaccharide-specific enhancer complex involving Ets, Elk-1, Sp1, and CREB binding protein and p300 is recruited to the tumor necrosis factor alpha promoter in vivo. Mol Cell Biol 20:6084–6094 [CrossRef]
     [Google Scholar]
  50. Xu Q., Musier-Forsyth K., Hammer R. P., Barany G. 1996; Use of 1,2,4-dithiazolidine-3,5-dione (DtsNH) and 3-ethoxy-1,2,4-dithiazoline-5-one (EDITH) for synthesis of phosphorothioate-containing oligodeoxyribonucleotides. Nucleic Acids Res 24:1602–1607 [CrossRef]
     [Google Scholar]
  51. Yang X., Fennewald S., Luxon B. A., Aronson J., Herzog N. K., Gorenstein D. G. 1999; Aptamers containing thymidine 3′-O-phosphorothioates: synthesis and binding to nuclear factor-B. Bioorg Med Chem Lett 9:3357–3362 [CrossRef]
     [Google Scholar]
  52. Yang X., Bassett S. E., Li X., Luxon B. A., Herzog N. K., Shope R. E., Aronson J., Prow T. W., Leary J. F. & other authors (2002a). Construction and selection of bead-bound combinatorial oligonucleoside phosphorothioate and phosphorodithioate aptamer libraries designed for rapid PCR-based sequencing. Nucleic Acids Res 30:e132 [CrossRef]
     [Google Scholar]
  53. Yang X., Hodge R. P., Luxon B. A., Shope R., Gorenstein D. G. 2002b; Separation of synthetic oligonucleotide dithioates from monothiophosphate impurities by anion-exchange chromatography on a mono-q column. Anal Biochem 306:92–99 [CrossRef]
     [Google Scholar]
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Thioaptamer decoy targeting of AP-1 proteins influences cytokine expression and the outcome of arenavirus infections
J. Gen. Virol. 88, 981 (2007); https://doi.org/10.1099/vir.0.82499-0
/content/journal/jgv/10.1099/vir.0.82499-0
/content/journal/jgv/10.1099/vir.0.82499-0
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