Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1995 Mar;69(3):1480–1484. doi: 10.1128/jvi.69.3.1480-1484.1995

Expression of influenza virus hemagglutinin activates transcription factor NF-kappa B.

H L Pahl 1, P A Baeuerle 1
PMCID: PMC188737  PMID: 7853480

Abstract

Influenza virus infection initiates transcription of a variety of genes for cytokines such as tumor necrosis factor alpha (TNF-alpha), TNF-beta, interleukin 1 alpha, (IL-1 alpha), IL-1 beta, IL-2, IL-4, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, and gamma interferon. However, the mechanism by which virus infection elicits cytokine expression remains unknown. Six influenza virus-induced cytokine genes are targets for the inducible transcription factor NF-kappa B, a central regulator of the human immune response. Here, we show that expression of a single influenza virus protein, the virion surface hemagglutinin, strongly activates NF-kappa B DNA binding and transactivation. Activation is inhibited in the presence of the antioxidant dithiothreitol, suggesting that, similar to the findings for previously described inducers of NF-kappa B, hemagglutinin expression generates radical oxygen intermediates which activate the transcription factor. Hemagglutinin is the first secretory and structural viral protein reported to activate NF-kappa B and thus represents a new class of inducers for this transcription factor. We discuss these results in the context of clinical complications of influenza virus infection.

Full Text

The Full Text of this article is available as a PDF (278.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Babiuk L. A., Lawman M. J., Ohmann H. B. Viral-bacterial synergistic interaction in respiratory disease. Adv Virus Res. 1988;35:219–249. doi: 10.1016/S0065-3527(08)60713-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baeuerle P. A., Baltimore D. I kappa B: a specific inhibitor of the NF-kappa B transcription factor. Science. 1988 Oct 28;242(4878):540–546. doi: 10.1126/science.3140380. [DOI] [PubMed] [Google Scholar]
  3. Baeuerle P. A., Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994;12:141–179. doi: 10.1146/annurev.iy.12.040194.001041. [DOI] [PubMed] [Google Scholar]
  4. Cerami A., Beutler B. The role of cachectin/TNF in endotoxic shock and cachexia. Immunol Today. 1988 Jan;9(1):28–31. doi: 10.1016/0167-5699(88)91353-9. [DOI] [PubMed] [Google Scholar]
  5. Gong J. H., Sprenger H., Hinder F., Bender A., Schmidt A., Horch S., Nain M., Gemsa D. Influenza A virus infection of macrophages. Enhanced tumor necrosis factor-alpha (TNF-alpha) gene expression and lipopolysaccharide-triggered TNF-alpha release. J Immunol. 1991 Nov 15;147(10):3507–3513. [PubMed] [Google Scholar]
  6. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  7. Hennet T., Ziltener H. J., Frei K., Peterhans E. A kinetic study of immune mediators in the lungs of mice infected with influenza A virus. J Immunol. 1992 Aug 1;149(3):932–939. [PubMed] [Google Scholar]
  8. Hinshaw V. S., Olsen C. W., Dybdahl-Sissoko N., Evans D. Apoptosis: a mechanism of cell killing by influenza A and B viruses. J Virol. 1994 Jun;68(6):3667–3673. doi: 10.1128/jvi.68.6.3667-3673.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Meyer M., Schreck R., Baeuerle P. A. H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor. EMBO J. 1993 May;12(5):2005–2015. doi: 10.1002/j.1460-2075.1993.tb05850.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  11. Pahl H. L., Burn T. C., Tenen D. G. Optimization of transient transfection into human myeloid cell lines using a luciferase reporter gene. Exp Hematol. 1991 Nov;19(10):1038–1041. [PubMed] [Google Scholar]
  12. Reisinger E. C., Kern P., Ernst M., Bock P., Flad H. D., Dietrich M. Inhibition of HIV progression by dithiocarb. German DTC Study Group. Lancet. 1990 Mar 24;335(8691):679–682. doi: 10.1016/0140-6736(90)90802-c. [DOI] [PubMed] [Google Scholar]
  13. Sarawar S. R., Doherty P. C. Concurrent production of interleukin-2, interleukin-10, and gamma interferon in the regional lymph nodes of mice with influenza pneumonia. J Virol. 1994 May;68(5):3112–3119. doi: 10.1128/jvi.68.5.3112-3119.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schreck R., Albermann K., Baeuerle P. A. Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Radic Res Commun. 1992;17(4):221–237. doi: 10.3109/10715769209079515. [DOI] [PubMed] [Google Scholar]
  15. Schreck R., Baeuerle P. A. A role for oxygen radicals as second messengers. Trends Cell Biol. 1991 Aug;1(2-3):39–42. doi: 10.1016/0962-8924(91)90072-h. [DOI] [PubMed] [Google Scholar]
  16. Schreck R., Meier B., Männel D. N., Dröge W., Baeuerle P. A. Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. J Exp Med. 1992 May 1;175(5):1181–1194. doi: 10.1084/jem.175.5.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schreck R., Rieber P., Baeuerle P. A. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J. 1991 Aug;10(8):2247–2258. doi: 10.1002/j.1460-2075.1991.tb07761.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sprenger H., Bacher M., Rischkowsky E., Bender A., Nain M., Gemsa D. Characterization of a high molecular weight tumor necrosis factor-alpha mRNA in influenza A virus-infected macrophages. J Immunol. 1994 Jan 1;152(1):280–289. [PubMed] [Google Scholar]
  19. Takizawa T., Matsukawa S., Higuchi Y., Nakamura S., Nakanishi Y., Fukuda R. Induction of programmed cell death (apoptosis) by influenza virus infection in tissue culture cells. J Gen Virol. 1993 Nov;74(Pt 11):2347–2355. doi: 10.1099/0022-1317-74-11-2347. [DOI] [PubMed] [Google Scholar]
  20. Yodoi J., Uchiyama T. Diseases associated with HTLV-I: virus, IL-2 receptor dysregulation and redox regulation. Immunol Today. 1992 Oct;13(10):405–411. doi: 10.1016/0167-5699(92)90091-K. [DOI] [PubMed] [Google Scholar]
  21. Zabel U., Henkel T., Silva M. S., Baeuerle P. A. Nuclear uptake control of NF-kappa B by MAD-3, an I kappa B protein present in the nucleus. EMBO J. 1993 Jan;12(1):201–211. doi: 10.1002/j.1460-2075.1993.tb05646.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES