Synergistic activation of human immunodeficiency virus type 1 promoter activity by NF-kappa B and inhibitors of deacetylases: Potential perspectives for the development of therapeutic strategies
[en] The transcription factor NF-kappaB plays a central role in the human immunodeficiency virus type 1 (HIV-1) activation pathway. HIV-1 transcription is also regulated by protein acetylation, since treatment with deacetylase inhibitors such as trichostatin A (TSA) or sodium butyrate (NaBut) markedly induces HIV-1 transcriptional activity of the long terminal repeat (LTR) promoter. Here, we demonstrate that TSA (NaBut) synergized with both ectopically expressed p50/p65 and tumor necrosis factor alpha/SF2 (TNF)-induced NF-kappaB to activate the LTR. This was confirmed for LTRs from subtypes A through G of the HIV-1 major group, with a positive correlation between the number Of kappaB sites present in the LTRs and the amplitude of the TNF-TSA synergism. Mechanistically, TSA (NaBut) delayed the cytoplasmic recovery of the inhibitory protein IkappaBalpha. This coincided with a prolonged intranuclear presence and DNA binding activity of NF-kappaB. The physiological relevance of the TNF-TSA (NaBut) synergism was shown on HIV-1 replication in both acutely and latently HIV-infected cell lines. Therefore, our results open new therapeutic strategies aimed at decreasing or eliminating the pool of latently HIV-infected reservoirs by forcing viral expression.
Research center :
Giga-Signal Transduction - ULiège
Disciplines :
Immunology & infectious disease
Author, co-author :
Quivy, Vincent
Adam, Emmanuelle
Collette, Yves
Demonte, Dominique
Chariot, Alain ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Synergistic activation of human immunodeficiency virus type 1 promoter activity by NF-kappa B and inhibitors of deacetylases: Potential perspectives for the development of therapeutic strategies
Publication date :
November 2002
Journal title :
Journal of Virology
ISSN :
0022-538X
eISSN :
1098-5514
Publisher :
Amer Soc Microbiology, Washington, United States - Washington
Adams, M., L. Sharmeen, J. Kimpton, J. M. Romeo, J. V. Garcia, B. M. Peterlin, M. Groudine, and M. Emerman. 1994. Cellular latency in human immunodeficiency virus-infected individuals with high CD4 levels can be detected by the presence of promoter-proximal transcripts. Proc. Natl. Acad. Sci. USA 91:3862-3866.
Ashburner, B. P., S. D. Westerheide, and A. S. Baldwin, Jr. 2001. The p65 (RelA) subunit of NF-KB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression. Mol. Cell. Biol. 21:7065-7077.
Chen, H., M. Tini, and R. M. Evans. 2001. HATs on and beyond chromatin. Curr. Opin. Cell Biol. 13:218-224.
Chen, L., W. Fischle, E. Verdin, and W. C. Greene. 2001. Duration of nuclear NF-κB action regulated by reversible acetylation. Science 293:1653-1657.
Chun, T. W., D. Engel, S. B. Mizell, L. A. Ehler, and A. S. Fauci. 1998. Induction of HIV-1 replication in latently infected CD4+ T cells using a combination of cytokines. J. Exp. Med. 188:83-91.
Cohen, J. 1998. Exploring how to get at and eradicate hidden HIV. Science 279:1854-1855.
Col, E., C. Caron, D. Seigneurin-Berny, J. Gracia, A. Favier, and S. Khochbin. 2001. The histone acetyltransferase, hGCN5, interacts with and acetylates the HIV transactivator, Tat. J. Biol. Chem. 276:28179-28184.
Collins, A. F., H. A. Pearson, P. Giardina, K. T. McDonagh, S. W. Brusilow, and G. J. Dover. 1995. Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a clinical trial. Blood 85:43-49.
Coull, J. J., F. Romerio, J. M. Sun, J. L. Volker, K. M. Galvin, J. R. Davie, Y. Shi, U. Hansen, and D. M. Margolis. 2000. The human factors YY1 and LSF repress the human immunodeficiency virus type 1 long terminal repeat via recruitment of histone deacetylase 1. J. Virol. 74:6790-6799.
Doetzlhofer, A., H. Rotheneder, G. Lagger, M. Koranda, V. Kurtev, G. Brosch, E. Wintersberger, and C. Seiser. 1999. Histone deacetylase I can repress transcription by binding to Spl. Mol. Cell. Biol. 19:5504-5511.
Dover, G. J., S. Brusilow, and S. Charache. 1994. Induction of fetal hemoglobin production in subjects with sickle cell anemia by oral sodium phenylbutyrate. Blood 84:339-343.
el Kharroubi, A., G. Piras, R. Zensen, and M. A. Martin. 1998. Transcriptional activation of the integrated chromatin-associated human immunodeficiency virus type 1 promoter. Mol. Cell. Biol. 18:2535-2544.
Emiliani, S., W. Fischle, M. Ott, C. Van Lint, C. A. Amella, and E. Verdin. 1998. Mutations in the rat gene are responsible for human immunodeficiency virus type 1 postintegration latency in the U1 cell line. J. Virol. 72:1666-1670.
Emiliani, S., C. Van Lint, W. Fischle, P. Paras, Jr., M. Ott, J. Brady, and E. Verdin. 1996. A point mutation in the HIV-1 Tat responsive element is associated with postintegration latency. Proc. Natl. Acad. Sci. USA 93:6377-6381.
Finzi, D., M. Hermankova, T. Pierson, L. M. Carruth, C. Buck, R. E. Chaisson, T. C. Quinn, K. Chadwick, J. Margolick, R. Brookmeyer, J. Gallant, M. Markowitz, D. D. Ho, D. D. Richman, and R. F. Siliciano. 1997. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278:1295-1300.
Folks, T. M., K. A. Clouse, J. Justement, A. Rabson, E. Duh, J. H. Kehrl, and A. S. Fauci. 1989. Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc. Natl. Acad. Sci. USA 86:2365-2368.
Gerritsen, M. E., A. J. Williams, A. S. Neish, S. Moore, Y. Shi, and T. Collins. 1997. CREB-binding protein/p300 are transcriptional coactivators of p65. Proc. Natl. Acad. Sci. USA 94:2927-2932.
Ghosh, S., M. J. May, and E. B. Kopp. 1998. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16:225-260.
Herschlag, D., and F. B. Johnson. 1993. Synergism in transcriptional activation: a kinetic view. Genes Dev. 7:173-179.
Igarashi, T., C. R. Brown, Y. Endo, A. Buckler-White, R. Plishka, N. Bischofberger, V. Hirsch, and M. A. Martin. 2001. Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type I chimera (SHIV): implications for HIV-1 infections of humans. Proc. Natl. Acad. Sci. USA 98:658-663.
Imhof, A., X. J. Yang, V. V. Ogryzko, Y. Nakatani, A. P. Wolffe, and H. Ge. 1997. Acetylation of general transcription factors by histone acetyltransferases. Curr. Biol. 7:689-692.
Israel, A. 2000. The IKK complex: an integrator of all signals that activate NF-κB? Trends Cell Biol. 10:129-133.
Jeeninga, R. E., M. Hoogenkamp, M. Armand-Ugon, M. de Baar, K. Verhoef, and B. Berkhout. 2000. Functional differences between the long terminal repeat transcriptional promoters of human immunodeficiency virus type 1 subtypes A through G. J. Virol. 74:3740-3751.
Jeong, S., and A. Stein. 1994. Micrococcal nuclease digestion of nuclei reveals extended nucleosome ladders having anomalous DNA lengths for chromatin assembled on non-replicating plasmids in transfected cells. Nucleic Acids Res. 22:370-375.
Johannessen, C. U. 2000. Mechanisms of action ofvalproate: a commentary. Neurochem. Int. 37:103-110.
Jordan, A., P. Defechereux, and E. Verdin. 2001. The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation. EMBO J. 20:1726-1738.
Karin, M. 1999. The beginning of the end: IκB kinase (IKK) and NF-κB activation. J. Biol. Chem. 274:27339-27342.
Karin, M., and Y. Ben Neriah. 2000. Phosphorylation meets ubiquitination: the control of NF-KB activity. Annu. Rev. Immunol. 18:621-663.
Khochbin, S., and H. Y. Kao. 2001. Histone deacetylase complexes: functional entities or molecular reservoirs. FEBS Lett. 494:141-144.
Kiernan, R. E., C. Vanhulle, L. Schiltz, E. Adam, H. Xiao, F. Maudoux, C. Calomme, A. Burny, Y. Nakatani, K. T. Jeang, M. Benkirane, and C. Van Lint. 1999. HIV-1 rat transcriptional activity is regulated by acetylation. EMBO J. 18:6106-6118.
Kouzarides, T. 2000. Acetylation: a regulatory modification to rival phosphorylation? EMBO J. 19:1176-1179.
Li, N., and M. Karin. 2000. Signaling pathways leading to nuclear factorkappa B activation. Methods Enzymol. 319:273-279.
McCune, J. M. 1995. Viral latency in HIV disease. Cell 82:183-188.
Mizzen, C. A., X. J. Yang, T. Kokubo, J. E. Brownell, A. J. Bannister, T. Owen-Hughes, J. Workman, L. Wang, S. L. Berger, T. Kouzarides, Y. Nakatani, and C. D. Allis. 1996. The TAF(II)250 subunit of TFIID has histone acetyltransferase activity. Cell 87:1261-1270.
Na, S. Y., S. K. Lee, S. J. Han, H. S. Choi, S. Y. Im, and J. W. Lee. 1998. Steroid receptor coactivator-1 interacts with the p50 subunit and coactivates nuclear factor κB-mediated transactivations. J. Biol. Chem. 273:10831-10834.
Navikas, V., J. Link, C. Persson, T. Olsson, B. Hojeberg, A. Ljungdahl, H. Link, and B. Wahren. 1995. Increased mRNA expression of IL-6, IL-10, TNF-alpha, and perforin in blood mononuclear cells in human HIV infection. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 9:484-489.
Osborn, L., S. Kunkel, and G. J. Nabel. 1989. Tumor necrosis factor alpha and interleukin I stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc. Natl. Acad. Sci. USA 86:2336-2340.
Pereira, L. A., K. Bentley, A. Peeters, M. J. Churchill, and N. J. Deacon. 2000. A compilation of cellular transcription factor interactions with the HIV-1 LTR promoter. Nucleic Acids Res. 28:663-668.
Perelson, A. S., P. Essunger, Y. Cao, M. Vesanen, A. Hurley, K. Saksela, M. Markowitz, and D. D. Ho. 1997. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 387:188-191.
Perkins, N. D., L. K. Felzien, J. C. Betts, K. Leung, D. H. Beach, and G. J. Nabel. 1997. Regulation of NF-KB by cyclin-dependent kinases associated with the p300 coactivator. Science 275:523-527.
Phiel, C. J., F. Zhang, E. Y. Huang, M. G. Guenther, M. A. Lazar, and P. S. Klein. 2001. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J. Biol. Chem. 276:36734-36741.
Pierson, T., J. McArthur, and R. F. Siliciano. 2000. Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annu. Rev. Immunol. 18:665-708.
Poli, G., A. Kinter, J. S. Justement, J. H. Kehrl, P. Bressler, S. Stanley, and A. S. Fauci. 1990. Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. Proc. Natl. Acad. Sci. USA 87:782-785.
a. Quivy, V., and C. Van Lint. 2002. Diversity of acetylation targets and roles in transcriptional regulation: the HIV-1 promoter as a model system. Biochem. Pharmacol. 64:925-934.
Rabson, A. B., and H. C. Lin. 2000. NF-kappa B and HIV: linking viral and immune activation. Adv. Pharmacol. 48:161-207.
Reeves, R., C. M. Gorman, and B. Howard. 1985. Minichromosome assembly of non-integrated plasmid DNA transfected into mammalian cells. Nucleic Acids Res. 13:3599-3615.
Roth, S. Y., J. M. Denu, and C. D. Allis. 2001. Histone acetyltransferases. Annu. Rev. Biochem. 70:81-120.
Schoonbroodt, S., V. Ferreira, M. Best-Belpomme, J. R. Boelaert, S. Legrand-Poels, M. Korner, and J. Piette. 2000. Crucial role of the aminoterminal tyrosine residue 42 and the carboxyl-terminal PEST domain of I kappa B alpha in NF-kappa B activation by an oxidative stress. J. Immunol. 164:4292-4300.
Sheridan, P. L., T. P. Mayall, E. Verdin, and K. A. Jones. 1997. Histone acetyltransferases regulate HIV-1 enhancer activity in vitro. Genes Dev. 11:3327-3340.
Steger, D. J., A. Eberharter, S. John, P. A. Grant, and J. L. Workman. 1998. Purified histone acetyltransferase complexes stimulate HIV-1 transcription from preassembled nucleosomal arrays. Proc. Natl. Acad. Sci. USA 95:12924-12929.
Suzuki, T., A. Kimura, R. Nagai, and M. Horikoshi. 2000. Regulation of interaction of the acetyltransferase region of p300 and the DNA-binding domain of Spl on and through DNA binding. Genes Cells 5:29-41.
Tunnicliff, G. 1999. Actions of sodium valproate on the central nervous system. J. Physiol. Pharmacol. 50:347-365.
Van Lint, C. 2000. Role of chromatin in HIV-1 transcriptional regulation. Adv. Pharmacol. 48:121-160.
Vanden Berghe, W., K. De Bosscher, E. Boone, S. Plaisance, and G. Haegeman. 2098. 1999. The nuclear factor-κB engages CBP/p300 and histone acetyltransferase activity for transcriptional activation of the interleukin-6 gene promoter. J. Biol. Chem. 274:32091-32093.
Van Lint, C., S. Emiliani, M. Ott, and E. Verdin. 1996. Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation. EMBO J. 15:1112-1120.
Van Lint, C., S. Emiliani, and E. Verdin. 1996. The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. Gene Expr. 5:245-253.
Van Lint, C., J. Ghysdael, P. Paras, Jr., A. Burny, and E. Verdin. 1994. A transcriptional regulatory element is associated with a nuclease-hypersensitive site in the pol gene of human immunodeficiency virus type 1. J. Virol. 68:2632-2648.
Van Lint, C., C. A. Amella, S. Emiliani, M. John, T. Jie, and E. Verdin. 1997. Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity. J. Virol. 71:6113-6127.
Verdin, E., P. Paras, Jr., and C. Van Lint. 1993. Chromatin disruption in the promoter of human immunodeficiency virus type I during transcriptional activation. EMBO J. 12:3249-3259.
West, M. J., A. D. Lowe, and J. Karn. 2001. Activation of human immunodeficiency virus transcription in T cells revisited: NF-KB p65 stimulates transcriptional elongation. J. Virol. 75:8524-8537.
Winslow, B. J., R. J. Pomerantz, O. Bagasra, and D. Trono. 1993. HIV-1 latency due to the site of proviral integration. Virology 196:849-854.
Wong, J. K., M. Hezareh, H. F. Gunthard, D. V. Havlir, C. C. Ignacio, C. A. Spina, and D. D. Richman. 1997. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278:1291-1295.
