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. 1993 Nov;67(11):6596–6604. doi: 10.1128/jvi.67.11.6596-6604.1993

Phosphatidylcholine hydrolysis activates NF-kappa B and increases human immunodeficiency virus replication in human monocytes and T lymphocytes.

F Arenzana-Seisdedos 1, B Fernandez 1, I Dominguez 1, J M Jacqué 1, D Thomas 1, M T Diaz-Meco 1, J Moscat 1, J L Virelizier 1
PMCID: PMC238097  PMID: 8411362

Abstract

We have tested whether breakdown of phosphatidylcholine (PC) initiated by exogenous addition of a PC-specific phospholipase C (PC-PLC) from Bacillus cereus or by endogenous overexpression of PC-PLC induces functional activation of NF-kappa B and increases human immunodeficiency virus (HIV) enhancer activity. PC-PLC-activated hydrolysis of PC was found to induce bona fide p50/p65 NF-kappa B binding activity in three different cell lines of human or murine origin. No significant changes in the turnover of other cellular phospholipids were detected in PC-PLC-treated cells. Induction of NF-kappa B by PC-PLC did not depend on de novo synthesis of proteins or autocrine secretion of either tumor necrosis factor or interleukin 1. In human monocytic and lymphoblastoid T-cell lines, induction of NF-kappa B by PC-PLC resulted in clear induction of luciferase expression vectors placed under the control of synthetic kappa B enhancers or wild type, but not kappa B-mutated, HIV long terminal repeat constructs. HIV replication was increased by PC-PLC in chronically infected monocytes and T lymphocytes. NF-kappa B activation promoted by addition of exogenous PC-PLC correlated with an intense production of diacylglycerol. However, addition of a phosphatidylinositol-specific PLC from B. cereus also induced diacylglycerol but did not activate kappa B enhancer-directed vectors. PC-PLC-induced NF-kappa B activation could not be blocked by a specific inhibitor of phorbol ester-inducible protein kinases C. These results indicate that a cellular transduction pathway, dependent on specific PC breakdown, is functional in T lymphocytes and monocytes and may be used by various transmembrane receptors to activate HIV transcription through NF-kappa B-dependent induction of the HIV enhancer.

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Selected References

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  1. Arenzana-Seisdedos F., Israël N., Bachelerie F., Hazan U., Alcami J., Dautry F., Virelizier J. L. c-Ha-ras transfection induces human immunodeficiency virus (HIV) transcription through the HIV-enhancer in human fibroblasts and astrocytes. Oncogene. 1989 Nov;4(11):1359–1362. [PubMed] [Google Scholar]
  2. Bachelerie F., Alcami J., Arenzana-Seisdedos F., Virelizier J. L. HIV enhancer activity perpetuated by NF-kappa B induction on infection of monocytes. Nature. 1991 Apr 25;350(6320):709–712. doi: 10.1038/350709a0. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Berry N., Ase K., Kishimoto A., Nishizuka Y. Activation of resting human T cells requires prolonged stimulation of protein kinase C. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2294–2298. doi: 10.1073/pnas.87.6.2294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berry N., Nishizuka Y. Protein kinase C and T cell activation. Eur J Biochem. 1990 Apr 30;189(2):205–214. doi: 10.1111/j.1432-1033.1990.tb15478.x. [DOI] [PubMed] [Google Scholar]
  6. Besterman J. M., Duronio V., Cuatrecasas P. Rapid formation of diacylglycerol from phosphatidylcholine: a pathway for generation of a second messenger. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6785–6789. doi: 10.1073/pnas.83.18.6785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chattopadhyay S. K., Oliff A. I., Linemeyer D. L., Lander M. R., Lowy D. R. Genomes of murine leukemia viruses isolated from wild mice. J Virol. 1981 Sep;39(3):777–791. doi: 10.1128/jvi.39.3.777-791.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Diaz-Laviada I., Larrodera P., Diaz-Meco M. T., Cornet M. E., Guddal P. H., Johansen T., Moscat J. Evidence for a role of phosphatidylcholine-hydrolysing phospholipase C in the regulation of protein kinase C by ras and src oncogenes. EMBO J. 1990 Dec;9(12):3907–3912. doi: 10.1002/j.1460-2075.1990.tb07611.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Diaz-Laviada I., Larrodera P., Nieto J. L., Cornet M. E., Diaz-Meco M. T., Sanchez M. J., Guddal P. H., Johansen T., Haro A., Moscat J. Mechanism of inhibition of adenylate cyclase by phospholipase C-catalyzed hydrolysis of phosphatidylcholine. Involvement of a pertussis toxin-sensitive G protein and protein kinase C. J Biol Chem. 1991 Jan 15;266(2):1170–1176. [PubMed] [Google Scholar]
  10. Diaz-Meco M. T., Berra E., Municio M. M., Sanz L., Lozano J., Dominguez I., Diaz-Golpe V., Lain de Lera M. T., Alcamí J., Payá C. V. A dominant negative protein kinase C zeta subspecies blocks NF-kappa B activation. Mol Cell Biol. 1993 Aug;13(8):4770–4775. doi: 10.1128/mcb.13.8.4770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dominguez I., Sanz L., Arenzana-Seisdedos F., Diaz-Meco M. T., Virelizier J. L., Moscat J. Inhibition of protein kinase C zeta subspecies blocks the activation of an NF-kappa B-like activity in Xenopus laevis oocytes. Mol Cell Biol. 1993 Feb;13(2):1290–1295. doi: 10.1128/mcb.13.2.1290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Exton J. H. Signaling through phosphatidylcholine breakdown. J Biol Chem. 1990 Jan 5;265(1):1–4. [PubMed] [Google Scholar]
  13. Feinberg M. B., Baltimore D., Frankel A. D. The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation. Proc Natl Acad Sci U S A. 1991 May 1;88(9):4045–4049. doi: 10.1073/pnas.88.9.4045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ghosh S., Baltimore D. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. Nature. 1990 Apr 12;344(6267):678–682. doi: 10.1038/344678a0. [DOI] [PubMed] [Google Scholar]
  15. Hazan U., Thomas D., Alcami J., Bachelerie F., Israel N., Yssel H., Virelizier J. L., Arenzana-Seisdedos F. Stimulation of a human T-cell clone with anti-CD3 or tumor necrosis factor induces NF-kappa B translocation but not human immunodeficiency virus 1 enhancer-dependent transcription. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7861–7865. doi: 10.1073/pnas.87.20.7861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Horvat R. T., Wood C. HIV promoter activity in primary antigen-specific human T lymphocytes. J Immunol. 1989 Oct 15;143(8):2745–2751. [PubMed] [Google Scholar]
  17. Israël N., Hazan U., Alcami J., Munier A., Arenzana-Seisdedos F., Bachelerie F., Israël A., Virelizier J. L. Tumor necrosis factor stimulates transcription of HIV-1 in human T lymphocytes, independently and synergistically with mitogens. J Immunol. 1989 Dec 15;143(12):3956–3960. [PubMed] [Google Scholar]
  18. Kieran M., Blank V., Logeat F., Vandekerckhove J., Lottspeich F., Le Bail O., Urban M. B., Kourilsky P., Baeuerle P. A., Israël A. The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product. Cell. 1990 Sep 7;62(5):1007–1018. doi: 10.1016/0092-8674(90)90275-j. [DOI] [PubMed] [Google Scholar]
  19. Kimura A., Israël A., Le Bail O., Kourilsky P. Detailed analysis of the mouse H-2Kb promoter: enhancer-like sequences and their role in the regulation of class I gene expression. Cell. 1986 Jan 31;44(2):261–272. doi: 10.1016/0092-8674(86)90760-9. [DOI] [PubMed] [Google Scholar]
  20. Lacal J. C., Moscat J., Aaronson S. A. Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene. Nature. 1987 Nov 19;330(6145):269–272. doi: 10.1038/330269a0. [DOI] [PubMed] [Google Scholar]
  21. Larrodera P., Cornet M. E., Diaz-Meco M. T., Lopez-Barahona M., Diaz-Laviada I., Guddal P. H., Johansen T., Moscat J. Phospholipase C-mediated hydrolysis of phosphatidylcholine is an important step in PDGF-stimulated DNA synthesis. Cell. 1990 Jun 15;61(6):1113–1120. doi: 10.1016/0092-8674(90)90074-o. [DOI] [PubMed] [Google Scholar]
  22. Liou H. C., Nolan G. P., Ghosh S., Fujita T., Baltimore D. The NF-kappa B p50 precursor, p105, contains an internal I kappa B-like inhibitor that preferentially inhibits p50. EMBO J. 1992 Aug;11(8):3003–3009. doi: 10.1002/j.1460-2075.1992.tb05370.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Liscovitch M. Crosstalk among multiple signal-activated phospholipases. Trends Biochem Sci. 1992 Oct;17(10):393–399. doi: 10.1016/0968-0004(92)90007-v. [DOI] [PubMed] [Google Scholar]
  24. Mathias S., Younes A., Kan C. C., Orlow I., Joseph C., Kolesnick R. N. Activation of the sphingomyelin signaling pathway in intact EL4 cells and in a cell-free system by IL-1 beta. Science. 1993 Jan 22;259(5094):519–522. doi: 10.1126/science.8424175. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y. Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties. Proc Natl Acad Sci U S A. 1989 May;86(9):3099–3103. doi: 10.1073/pnas.86.9.3099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Paya C. V., Ten R. M., Bessia C., Alcami J., Hay R. T., Virelizier J. L. NF-kappa B-dependent induction of the NF-kappa B p50 subunit gene promoter underlies self-perpetuation of human immunodeficiency virus transcription in monocytic cells. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7826–7830. doi: 10.1073/pnas.89.16.7826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Price B. D., Morris J. D., Marshall C. J., Hall A. Stimulation of phosphatidylcholine hydrolysis, diacylglycerol release, and arachidonic acid production by oncogenic ras is a consequence of protein kinase C activation. J Biol Chem. 1989 Oct 5;264(28):16638–16643. [PubMed] [Google Scholar]
  29. Rosoff P. M., Savage N., Dinarello C. A. Interleukin-1 stimulates diacylglycerol production in T lymphocytes by a novel mechanism. Cell. 1988 Jul 1;54(1):73–81. doi: 10.1016/0092-8674(88)90181-x. [DOI] [PubMed] [Google Scholar]
  30. Ruben S. M., Dillon P. J., Schreck R., Henkel T., Chen C. H., Maher M., Baeuerle P. A., Rosen C. A. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991 Mar 22;251(5000):1490–1493. doi: 10.1126/science.2006423. [DOI] [PubMed] [Google Scholar]
  31. Schütze S., Berkovic D., Tomsing O., Unger C., Krönke M. Tumor necrosis factor induces rapid production of 1'2'diacylglycerol by a phosphatidylcholine-specific phospholipase C. J Exp Med. 1991 Nov 1;174(5):975–988. doi: 10.1084/jem.174.5.975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Siekevitz M., Josephs S. F., Dukovich M., Peffer N., Wong-Staal F., Greene W. C. Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-I. Science. 1987 Dec 11;238(4833):1575–1578. doi: 10.1126/science.2825351. [DOI] [PubMed] [Google Scholar]
  33. Stewart S. J., Cunningham G. R., Strupp J. A., House F. S., Kelley L. L., Henderson G. S., Exton J. H., Bocckino S. B. Activation of phospholipase D: a signaling system set in motion by perturbation of the T lymphocyte antigen receptor/CD3 complex. Cell Regul. 1991 Oct;2(10):841–850. doi: 10.1091/mbc.2.10.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Toullec D., Pianetti P., Coste H., Bellevergue P., Grand-Perret T., Ajakane M., Baudet V., Boissin P., Boursier E., Loriolle F. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem. 1991 Aug 25;266(24):15771–15781. [PubMed] [Google Scholar]
  35. Virelizier J. L. Cellular activation and human immunodeficiency virus infection. Curr Opin Immunol. 1989;2(3):409–413. doi: 10.1016/0952-7915(89)90151-9. [DOI] [PubMed] [Google Scholar]

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