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Volume 79, Issue 11

NF-kappaB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-gamma-induced nitric oxide production in macrophages Free

Abstract

Nitric oxide (NO), produced in interferon (IFN)-- activated murine macrophages by the enzyme inducible nitric oxide synthase (iNOS), has been found to have antiviral properties. We have previously shown that herpes simplex virus type 2 (HSV-2) infection of macrophages synergistically enhances IFN--induced NO production, and we now extend these findings by providing evidence that virus- induced tumour necrosis factor (TNF)-α mediates activation of the transcription factor nuclear factor (NF)-B, which in turn is responsible for the synergistic effect. HSV-2 infection and IFN- stimulation of macrophages synergistically induced TNF-α secretion and nuclear translocation of NF-B, which bound to a sequence corresponding to a B site in the iNOS promoter. The effect of HSV-2 on NF-B and NO production was eliminated when cells were treated with antibodies to TNF-α, and direct inhibition of NF-B activation with pyrrolidinedithio- carbamate (PDTC) also blocked the effect of HSV-2 infection on NO production. The effect of the NF-B activation inhibitor was not mediated through inhibition of the production of interferon regulatory factor (IRF)-1 or of TNF-α itself, and a possible alternative mechanism of activation of NF-B through virus-induced activation of the kinase PKR was also ruled out. Thus, our data indicate that NF-B activation, through virus-induced autocrine TNF-α secretion, is responsible for the synergistic effect of HSV-2 infection on IFN--induced NO production, and that such activation might constitute a mechanism by which high-output NO production is targeted to infectious foci.

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© Society for General Microbiology 1998
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1998-11-01
2024-04-24
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References

  1. Adler H., Beland J. L., Del-Pan N. C., Kobzik L., Brewer J. P., Martin T. R., Rimm I. J. 1997; Suppression of herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition of inducible nitric oxide synthase (iNOS, NOS2). Journal of Experimental Medicine 185:1533–1540
     [Google Scholar]
  2. Baldwin A. S. Jr 1996; The NF-kB and IkB proteins: new discoveries and insights. Annual Review of Immunology 14:649–683
     [Google Scholar]
  3. Baskin H., Ellermann-Eriksen S., Lovmand J., Mogensen S. C. 1997; Herpes simplex virus type 2 synergizes with interferon-γ in the induction of nitric oxide production in mouse macrophages through autocrine secretion oftumour necrosis factor-α. Journal of General Virology 78:195–203
     [Google Scholar]
  4. Beauparlant P., Hiscott J. 1996; Biological and biochemical inhibitors ofthe NF-kB/Rel proteins and cytokine synthesis. Cytokine and Growth Factor Reviews 7:175–190
     [Google Scholar]
  5. Beg A. A., Sha W. C., Bronson R. T., Ghosh S., Baltimore D. 1995; Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kB. Nature 376:167–170
     [Google Scholar]
  6. Boehm U., Klamp T., Groot M., Howard J. C. 1997; Cellular responses to interferon-γ. Annual Review of Immunology 15:749–795
     [Google Scholar]
  7. Collart M. A., Baeuerle P., Vassalli P. 1990; Regulation of tumor necrosis factor α transcription in macrophages: involvement of four kB-like motifs and of constitutive and inducible forms of NF-kB. Molecular and Cellular Biology 10:1498–1506
     [Google Scholar]
  8. Croen K. D. 1993; Evidence for an antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication. Journal of Clinical Investigation 91:2446–2452
     [Google Scholar]
  9. DeLuca C., Roulston A., Koromilas A., Wainberg M. A., Hiscott J. 1996; Chronic human immunodeficiency virus type 1 infection of myeloid cells disrupts the autoregulatory control of the NF-kB/Rel pathway via enhanced IkBa degradation. Journal of Virology 70:5183–5193
     [Google Scholar]
  10. Ding A. H., Nathan C., Stuehr D. J. 1988; Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. Journal of Immunology 141:2407–2412
     [Google Scholar]
  11. Drew P. D., Franzoso G., Becker K. G., Bours V., Carlson L. M., Siebenlist U., Ozato K. 1995; NFkB and interferon regulatory factor 1 physically interact and synergistically induce major histocompatibility class I gene expression. Journal of Interferon and Cytokine Research 15:1037–1045
     [Google Scholar]
  12. Elia A., Laing K. G., Schofield A., Tilleray V. J., Clemens M. J. 1996; Regulation of the double-stranded RNA-dependent protein kinase PKR by RNAs encoded by a repeated sequence in the Epstein-Barr virus genome. Nucleic Acids Research 24:4471–4478
     [Google Scholar]
  13. Ellermann-Eriksen S. 1993; Autocrine secretion of interferon-α/β and tumour necrosis factor-α synergistically activates mouse macrophages after infection with herpes simplex virus type 2. Journal of General Virology 74:2191–2199
     [Google Scholar]
  14. Garoufalis E., Kwan I., Lin R., Mustafa A., Pepin N., Roulston A., Lacoste J., Hiscott J. 1994; Viral induction of the human β interferon promoter: modulation of transcription by NF-kB/rel proteins and interferon regulatory factors. Journal of Virology 68:4707–4715
     [Google Scholar]
  15. Harada H., Takahashi E., Itoh S., Harada K., Hori T. A., Taniguchi T. 1994; Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes : implications for a gene network in the interferon system. Molecular and Cellular Biology 14:1500–1509
     [Google Scholar]
  16. Hauf N., Goebel W., Fiedler F., Sokolovic Z., Kuhn M. 1997; Listeria monocytogenes infection of P388D1 macrophages results in a biphasic NF-kB (RelA/p50) activation induced by lipoteichoic acid and bacterial phospholipases and mediated by IkBa and IkBβ degradation. Proceedings of the National Academy of Sciences, USA 94:9394–9399
     [Google Scholar]
  17. Kamijo R., Harda H., Matsuyama T., Bosland M., Gerecitano J., Shapiro D., Le J., Koh S. I., Kimura T., Green S. J., Mak T. W., Taniguchi T., Vilcek J. 1994; Requirement for transcription factor IRF-1 in NOS induction. Science 263:1612–1615
     [Google Scholar]
  18. Kang S. M., Tran A. C., Grilli M., Lenardo M. J. 1992; NF-kB subunit regulation in nontransformed CD4+ T lymphocytes. Science 256:1452–1456
     [Google Scholar]
  19. Karupiah G., Harris N. 1995; Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites. Journal of Experimental Medicine 181:2171–2179
     [Google Scholar]
  20. Karupiah G., Xie Q., Buller R. M. L., Nathan C., Duate C., MacMicking J. 1993; Inhibition of viral replication by interferon-γ-induced nitric oxide synthase. Science 261:1445–1448
     [Google Scholar]
  21. Lowenstein C. J., Alley E. W., Raval P., Snowman A. M., Snyder S. H., Russell S. W., Murphy W. J. 1993; Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon γ and lipopolysaccharide. Proceedings of the National Academy of Sciences, USA 90:9730–9734
     [Google Scholar]
  22. MacLean A., Wei X.-Q., Huang F.-P., Al-Alem U. A. H., Chan W. L., Liew F. Y. 1998; Mice lacking inducible nitric-oxide synthase are more susceptible to herpes simplex virus infection despite enhanced Th1 cell responses. Journal of General Virology 79:825–830
     [Google Scholar]
  23. Maran A., Maitra R. K., Kumar A., Dong B., Xiao W., Li G., Williams B. R., Torrence P. F., Silverman R. H. 1994; Blockage of NF-kB signaling by selective ablation of an mRNA target by 2-5A antisense chimeras. Science 265:789–792
     [Google Scholar]
  24. Melkova Z., Esteban M. 1995; Inhibition of vaccinia virus DNA replication by inducible expression of nitric oxide synthase. Journal of Immunology 155:5711–5718
     [Google Scholar]
  25. Mogensen S. C. 1979; Role of macrophages in natural resistance to virus infections. Microbiological Reviews 43:1–26
     [Google Scholar]
  26. Moncada S., Higgs A. 1993; The l-arginine-nitric oxide pathway. New England Journal of Medicine 329:2002–2012
     [Google Scholar]
  27. Morahan P. S., Dempsey W. L., Volkman A., Connor J. 1986; Antimicrobial activity of various immunomodulators : independence from normal levels of circulating monocytes and natural killer cells. Infection and Immunity 51:87–93
     [Google Scholar]
  28. Nathan C. F., Hibbs J. B. Jr 1994; Role of nitric oxide synthesis in macrophage antimicrobial activity. Current Opinion in Immunology 3:65–69
     [Google Scholar]
  29. Neish A. S., Read M. A., Thanos D., Pine R., Maniatis T., Collins T. 1995; Endothelial interferon regulatory factor 1 cooperates with NF-kB as a transcriptional activator of vascular cell adhesion molecule 1. Molecular and Cellular Biology 15:2558–2569
     [Google Scholar]
  30. Ohmori Y., Schreiber R. D., Hamilton T. A. 1997; Synergy between interferon-y and tumor necrosis factor-α in transcriptional activation is mediated by cooperation between signal transducer and activator of transcription 1 and nuclear factor kB. Journal of Biological Chemistry 272:14899–14907
     [Google Scholar]
  31. Paludan S. R., Lovmand J., Ellermann-Eriksen S., Mogensen S. C. 1997; Effect of IL-4 and IL-13 on IFN-γ-induced production of nitric oxide in mouse macrophages infected with herpes simplex virus type 2. FEBS Letters 414:61–64
     [Google Scholar]
  32. Pinto A. J., Stewart D., van Rooijen N., Morahan P. S. 1991; Selective depletion of liver and splenic macrophages using liposomes encapsulating the drug dichloromethylene diphosphonate : effects on antimicrobial resistance. Journal of Leukocyte Biology 49:579–586
     [Google Scholar]
  33. Schutze S., Wiegmann K., Machleidt T., Kronke M. 1995; TNF-induced activation of NF-kB. Immunobiology 193:193–203
     [Google Scholar]
  34. Spriggs M. K. 1996; One step ahead of the game: viral immuno-modulatory molecules. Annual Review of Immunology 14:101–130
     [Google Scholar]
  35. Szabo C., Ohshima H. 1997; DNA damage induced by peroxy- nitrite: subsequent biological effects. Nitric Oxide 1:373–385
     [Google Scholar]
  36. Xie Q., Kashiwabara Y., Nathan C. 1994; Role of transcription factor NF-kB in induction of NOS. Journal of Biological Chemistry 269:4705–4708
     [Google Scholar]
  37. Xie Q. W., Whisnant R., Nathan C. 1993; Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon and bacterial lipopolysaccharide. Journal of Experimental Medicine 177:1779–1784
     [Google Scholar]
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NF-kappaB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-gamma-induced nitric oxide production in macrophages
J. Gen. Virol. 79, 2785 (1998); https://doi.org/10.1099/0022-1317-79-11-2785
/content/journal/jgv/10.1099/0022-1317-79-11-2785
/content/journal/jgv/10.1099/0022-1317-79-11-2785
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