BET bromodomain inhibition as a novel strategy for reactivation of HIV-1

Journal of Leukocyte Biology

Volumn 92, Issue 6, 2012, Pages 1147-1154

  Banerjee, Camellia ^a   Archin, Nancie ^d   Michaels, Daniel ^a   Belkina, Anna C ^a   Denis, Gerald V ^a   Bradner, James ^c   Sebastiani, Paola ^b   Margolis, David M ^d   Montano, Monty ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

Cyclin; Histone deacetylase; qRT PCR; Tat

Indexed keywords

ANTINEOPLASTIC AGENT; CD28 ANTIGEN; CD3 ANTIGEN; CHEMOKINE RECEPTOR CXCR4; HISTONE DEACETYLASE 6; HISTONE DEACETYLASE INHIBITOR; JQ 1; PROTEIN INHIBITOR; SIRTUIN 1; UNCLASSIFIED DRUG;

ARTICLE; CD4+ T LYMPHOCYTE; CELL ISOLATION; CELL PROLIFERATION; HISTONE MODIFICATION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; PRIORITY JOURNAL; PROTEIN PROCESSING; UPREGULATION; VIRUS REACTIVATION; VIRUS REPLICATION; VIRUS TRANSCRIPTION;

AZEPINES; CD4-POSITIVE T-LYMPHOCYTES; CELL LINE; CELL PROLIFERATION; CHROMATIN ASSEMBLY AND DISASSEMBLY; CLUSTER ANALYSIS; GENE EXPRESSION REGULATION; GENE EXPRESSION REGULATION, VIRAL; HIV-1; HUMANS; LYMPHOCYTE ACTIVATION; MONOCYTE-MACROPHAGE PRECURSOR CELLS; TRANSCRIPTION, GENETIC; TRANSCRIPTOME; TRIAZOLES; VIRUS ACTIVATION; VIRUS LATENCY;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84867758122     PISSN: 07415400     EISSN: 19383673     Source Type: Journal    
DOI: 10.1189/jlb.0312165     Document Type: Article

References (58)

1. Dornadula, G., Zhang, H., VanUitert, B., Stern, J., Livornese Jr., L., Ingerman, M. J., Witek, J., Kedanis, R. J., Natkin, J., DeSimone, J., Pomerantz, R. J. (1999) Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. JAMA 282, 1627-1632.
2. Hatano, H., Delwart, E. L., Norris, P. J., Lee, T. H., Neilands, T. B., Kelley, C. F., Hunt, P. W., Hoh, R., Linnen, J. M., Martin, J. N., Busch, M. P., Deeks, S. G. (2010) Evidence of persistent low-level viremia in long-term HAART-suppressed, HIV-infected individuals. AIDS 24, 2535-2539.
3. Maldarelli, F., Palmer, S., King, M. S., Wiegand, A., Polis, M. A., Mican, J., Kovacs, J. A., Davey, R. T., Rock-Kress, D., Dewar, R., Liu, S., Metcalf, J. A., Rehm, C., Brun, S. C., Hanna, G. J., Kempf, D. J., Coffin, J. M., Mellors, J. W. (2007) ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 3, e46.
4. Nettles, R. E., Kieffer, T. L., Kwon, P., Monie, D., Han, Y., Parsons, T., Cofrancesco Jr., J., Gallant, J. E., Quinn, T. C., Jackson, B., Flexner, C., Carson, K., Ray, S., Persaud, D., Siliciano, R. F. (2005) Intermittent HIV-1 viremia (Blips) and drug resistance in patients receiving HAART. JAMA 293, 817-829.
5. Palmer, S., Wiegand, A. P., Maldarelli, F., Bazmi, H., Mican, J. M., Polis, M., Dewar, R. L., Planta, A., Liu, S., Metcalf, J. A., Mellors, J. W., Coffin, J. M. (2003) New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J. Clin. Microbiol. 41, 4531-4536.
6. Persaud, D., Siberry, G. K., Ahonkhai, A., Kajdas, J., Monie, D., Hutton, N., Watson, D. C., Quinn, T. C., Ray, S. C., Siliciano, R. F. (2004) Continued production of drug-sensitive human immunodeficiency virus type 1 in children on combination antiretroviral therapy who have undetectable viral loads. J. Virol. 78, 968-979.
7. Trono, D., Van Lint, C., Rouzioux, C., Verdin, E., Barre-Sinoussi, F., Chun, T. W., Chomont, N. (2010) HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science 329, 174-180.
8. Wong, J. K., Hezareh, M., Gunthard, H. F., Havlir, D. V., Ignacio, C. C., Spina, C. A., Richman, D. D. (1997) Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278, 1291-1295.
9. Finzi, D., Hermankova, M., Pierson, T., Carruth, L. M., Buck, C., Chaisson, R. E., Quinn, T. C., Chadwick, K., Margolick, J., Brookmeyer, R., Gallant, J., Markowitz, M., Ho, D. D., Richman, D. D., Siliciano, R. F. (1997) Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278, 1295-1300.
10. Chun, T. W., Carruth, L., Finzi, D., Shen, X., DiGiuseppe, J. A., Taylor, H., Hermankova, M., Chadwick, K., Margolick, J., Quinn, T. C., Kuo, Y. H., Brookmeyer, R., Zeiger, M. A., Barditch-Crovo, P., Siliciano, R. F. (1997) Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387, 183-188.
11. Hermankova, M., Siliciano, J. D., Zhou, Y., Monie, D., Chadwick, K., Margolick, J. B., Quinn, T. C., Siliciano, R. F. (2003) Analysis of human immunodeficiency virus type 1 gene expression in latently infected resting CD4+ T lymphocytes in vivo. J. Virol. 77, 7383-7392.
12. Bosque, A., Planelles, V. (2009) Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells. Blood 113, 58-65.
13. Tyagi, M., Pearson, R. J., Karn, J. (2010) Establishment of HIV latency in primary CD4+ cells is due to epigenetic transcriptional silencing and P-TEFb restriction. J. Virol. 84, 6425-6437.
14. Coull, J. J., Romerio, F., Sun, J. M., Volker, J. L., Galvin, K. M., Davie, J. R., Shi, Y., Hansen, U., Margolis, D. M. (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.
15. Van Lint, C., Emiliani, S., Ott, M., Verdin, E. (1996) Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation. EMBO J. 15, 1112-1120.
16. Ylisastigui, L., Archin, N. M., Lehrman, G., Bosch, R. J., Margolis, D. M. (2004) Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression. AIDS 18, 1101-1108.
17. Prins, J. M., Jurriaans, S., van Praag, R. M., Blaak, H., van Rij, R., Schellekens, P. T., ten Berge, I. J., Yong, S. L., Fox, C. H., Roos, M. T., de Wolf, F., Goudsmit, J., Schuitemaker, H., Lange, J. M. (1999) Im- muno-activation with anti-CD3 and recombinant human IL-2 in HIV-1- infected patients on potent antiretroviral therapy. AIDS 13, 2405-2410.
18. Bowman, M. C., Archin, N. M., Margolis, D. M. (2009) Pharmaceutical approaches to eradication of persistent HIV infection. Expert Rev. Mol. Med. 11, e6.
19. Choudhary, S. K., Archin, N. M., Margolis, D. M. (2008) Hexamethylbisacetamide and disruption of human immunodeficiency virus type 1 latency in CD4(+) T cells. J. Infect. Dis. 197, 1162-1170.
20. Lehrman, G., Hogue, I. B., Palmer, S., Jennings, C., Spina, C. A., Wiegand, A., Landay, A. L., Coombs, R. W., Richman, D. D., Mellors, J. W., Coffin, J. M., Bosch, R. J., Margolis, D. M. (2005) Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet 366, 549-555.
21. Siliciano, J. D., Lai, J., Callender, M., Pitt, E., Zhang, H., Margolick, J. B., Gallant, J. E., Cofrancesco, Jr. J., Moore, R. D., Gange, S. J., Siliciano, R. F. (2007) Stability of the latent reservoir for HIV-1 in patients receiving valproic acid. J. Infect. Dis. 195, 833-836.
22. Sagot-Lerolle, N., Lamine, A., Chaix, M. L., Boufassa, F., Aboulker, J. P., Costagliola, D., Goujard, C., Pallier, C., Delfraissy, J. F., Lambotte, O. (2008) Prolonged valproic acid treatment does not reduce the size of latent HIV reservoir. AIDS 22, 1125-1129.
23. Archin, N. M., Cheema, M., Parker, D., Wiegand, A., Bosch, R. J., Coffin, J. M., Eron, J., Cohen, M., Margolis, D. M. (2010) Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection. PLoS ONE 5, e9390.
24. Matalon, S., Rasmussen, T. A., Dinarello, C. A. (2011) Histone deacetylase inhibitors for purging HIV-1 from the latent reservoir. Mol. Med. 17, 466-472.
25. Antoni, B. A., Rabson, A. B., Kinter, A., Bodkin, M., Poli, G. (1994) NF-+B-dependent and -independent pathways of HIV activation in a chronically infected T cell line. Virology 202, 684-694.
26. Folks, T. M., Justement, J., Kinter, A., Dinarello, C. A., Fauci, A. S. (1987) Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science 238, 800-802.
27. Han, Y., Wind-Rotolo, M., Yang, H. C., Siliciano, J. D., Siliciano, R. F. (2007) Experimental approaches to the study of HIV-1 latency. Nat. Rev. Microbiol. 5, 95-106.
28. Jordan, A., Bisgrove, D., Verdin, E. (2003) HIV reproducibly establishes a latent infection after acute infection of T cells in vitro. EMBO J. 22, 1868-1877.
29. Williams, S. A., Kwon, H., Chen, L. F., Greene, W. C. (2007) Sustained induction of NF-κB is required for efficient expression of latent human immunodeficiency virus type 1. J. Virol. 81, 6043-6056.
30. Weinberger, L. S., Burnett, J. C., Toettcher, J. E., Arkin, A. P., Schaffer, D. V. (2005) Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Cell 122, 169-182.
31. Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., Philpott, M., Munro, S., McKeown, M. R., Wang, Y., Christie, A. L., West, N., Cameron, M. J., Schwartz, B., Heightman, T. D., La Thangue, N., French, C. A., Wiest, O., Kung, A. L., Knapp, S., Bradner, J. E. (2010) Selective inhibition of BET bromodomains. Nature 468, 1067-1073.
32. Bisgrove, D. A., Mahmoudi, T., Henklein, P., Verdin, E. (2007) Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription. Proc. Natl. Acad. Sci. USA 104, 13690-13695.
33. Malnati, M. S., Scarlatti, G., Gatto, F., Salvatori, F., Cassina, G., Rutigliano, T., Volpi, R., Lusso, P. (2008) A universal real-time PCR assay for the quantification of group-M HIV-1 proviral load. Nat. Protoc. 3, 1240-1248.
34. Archin, N. M., Eron, J. J., Palmer, S., Hartmann-Duff, A., Martinson, J. A., Wiegand, A., Bandarenko, N., Schmitz, J. L., Bosch, R. J., Landay, A. L., Coffin, J. M., Margolis, D. M. (2008) Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells. AIDS 22, 1131-1135.
35. Hosack, D. A., Dennis Jr., G., Sherman, B. T., Lane, H. C., Lempicki, R. A. (2003) Identifying biological themes within lists of genes with EASE. Genome Biol. 4, R70.
36. Lempicki, R. A., Polis, M. A., Yang, J., McLaughlin, M., Koratich, C., Huang, D. W., Fullmer, B., Wu, L., Rehm, C. A., Masur, H., Lane, H. C., Sherman, K. E., Fauci, A. S., Kottilil, S. (2006) Gene expression profiles in hepatitis C virus (HCV) and HIV coinfection: class prediction analyses before treatment predict the outcome of anti-HCV therapy among HIV-coinfected persons. J. Infect. Dis. 193, 1172-1177.
37. Duverger, A., Jones, J., May, J., Bibollet-Ruche, F., Wagner, F. A., Cron, R. Q., Kutsch, O. (2009) Determinants of the establishment of human immunodeficiency virus type 1 latency. J. Virol. 83, 3078.
38. Williams, S. A., Chen, L. F., Kwon, H., Ruiz-Jarabo, C. M., Verdin, E., Greene, W. C. (2006) NF-κB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J. 25, 139-149.
39. Mochizuki, K., Nishiyama, A., Jang, M. K., Dey, A., Ghosh, A., Tamura, T., Natsume, H., Yao, H., Ozato, K. (2008) The bromodomain protein Brd4 stimulates G1 gene transcription and promotes progression to S phase. J. Biol. Chem. 283, 9040-9048.
40. Moreira, J. M., Scheipers, P., Sorensen, P. (2003) The histone deacetylase inhibitor trichostatin A modulates CD4+ T cell responses. BMC Cancer 3, 30.
41. Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., Kastritis, E., Gilpatrick, T., Paranal, R. M., Qi, J., Chesi, M., Schinzel, A. C., McKeown, M. R., Heffernan, T. P., Vakoc, C. R., Bergsagel, P. L., Ghobrial, I. M., Richardson, P. G., Young, R. A., Hahn, W. C., Anderson, K. C., Kung, A. L., Bradner, J. E., Mitsiades, C. S. (2011) BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146, 904-917.
42. Peart, M. J., Smyth, G. K., van Laar, R. K., Bowtell, D. D., Richon, V. M., Marks, P. A., Holloway, A. J., Johnstone, R. W. (2005) Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors. Proc. Natl. Acad. Sci. USA 102, 3697-3702.
43. Ott, M., Geyer, M., Zhou, Q. (2011) The control of HIV transcription: keeping RNA polymerase II on track. Cell Host Microbe 10, 426-435.
44. Rao, J. N., Neumann, L., Wenzel, S., Schweimer, K., Rosch, P., Wohrl, B. M. (2006) Structural studies on the RNA-recognition motif of NELF E, a cellular negative transcription elongation factor involved in the regulation of HIV transcription. Biochem. J. 400, 449-456.
45. Fujinaga, K., Irwin, D., Huang, Y., Taube, R., Kurosu, T., Peterlin, B. M. (2004) Dynamics of human immunodeficiency virus transcription: PTEFb phosphorylates RD and dissociates negative effectors from the transactivation response element. Mol. Cell. Biol. 24, 787-795.
46. Zhang, Z., Klatt, A., Gilmour, D. S., Henderson, A. J. (2007) Negative elongation factor NELF represses human immunodeficiency virus transcription by pausing the RNA polymerase II complex. J. Biol. Chem. 282, 16981-16988.
47. Xie, B., Invernizzi, C. F., Richard, S., Wainberg, M. A. (2007) Arginine methylation of the human immunodeficiency virus type 1 Tat protein by PRMT6 negatively affects Tat interactions with both cyclin T1 and the Tat transactivation region. J. Virol. 81, 4226-4234.
48. Van Duyne, R., Easley, R., Wu, W., Berro, R., Pedati, C., Klase, Z., Kehn- Hall, K., Flynn, E. K., Symer, D. E., Kashanchi, F. (2008) Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR. Retrovirology 5, 40.
49. Sakane, N., Kwon, H.S., Pagans, S., Kaehlcke, K., Mizusawa, Y., Kamada, M., Lassen, K.G., Chan, J., Greene, W.C., Schnoelzer, M., Ott, M. (2011) Activation of HIV transcription by the viral Tat protein requires a demethylation step mediated by lysine-specific demethylase 1 (LSD1/ KDM1). PLoS Pathog. 7, e1002184.
50. Pagans, S., Pedal, A., North, B. J., Kaehlcke, K., Marshall, B. L., Dorr, A., Hetzer-Egger, C., Henklein, P., Frye, R., McBurney, M. W., Hruby, H., Jung, M., Verdin, E., Ott, M. (2005) SIRT1 regulates HIV transcription via Tat deacetylation. PLoS Biol. 3, e41.
51. Van Praag, R. M., Prins, J. M., Roos, M. T., Schellekens, P. T., Ten Berge, I. J., Yong, S. L., Schuitemaker, H., Eerenberg, A. J., Jurriaans, S., de Wolf, F., Fox, C. H., Goudsmit, J., Miedema, F., Lange, J. M. (2001) OKT3 and IL-2 treatment for purging of the latent HIV-1 reservoir in vivo results in selective long-lasting CD4+ T cell depletion. J. Clin. Immunol. 21, 218-226.
52. Richman, D. D., Margolis, D. M., Delaney, M., Greene, W. C., Hazuda, D., Pomerantz, R. J. (2009) The challenge of finding a cure for HIV infection. Science 323, 1304-1307.
53. Leoni, F., Zaliani, A., Bertolini, G., Porro, G., Pagani, P., Pozzi, P., Dona, G., Fossati, G., Sozzani, S., Azam, T., Bufler, P., Fantuzzi, G., Goncharov, I., Kim, S. H., Pomerantz, B. J., Reznikov, L. L., Siegmund, B., Dinarello, C. A., Mascagni, P. (2002) The antitumor histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits antiinflammatory properties via suppression of cytokines. Proc. Natl. Acad. Sci. USA 99, 2995-3000.
54. Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., Mayo, M. W. (2004) Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23, 2369-2380.
55. Huang, B., Yang, X. D., Zhou, M. M., Ozato, K., Chen, L. F. (2009) Brd4 coactivates transcriptional activation of NF-κ B via specific binding to acetylated RelA. Mol. Cell. Biol. 29, 1375-1387.
56. Mertz, J. A., Conery, A. R., Bryant, B. M., Sandy, P., Balasubramanian, S., Mele, D. A., Bergeron, L., Sims III, R. J. (2011) Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc. Natl. Acad. Sci. USA 108, 16669-16674.
57. Michels, A. A., Fraldi, A., Li, Q., Adamson, T. E., Bonnet, F., Nguyen, V. T., Sedore, S. C., Price, J. P., Price, D. H., Lania, L., Bensaude, O. (2004) Binding of the 7SK snRNA turns the HEXIM1 protein into a PTEFb (CDK9/cyclin T) inhibitor. EMBO J. 23, 2608-2619.
58. Jiang, G., Espeseth, A., Hazuda, D. J., Margolis, D. M. (2007) c-Myc and Sp1 contribute to proviral latency by recruiting histone deacetylase 1 to the human immunodeficiency virus type 1 promoter. J. Virol. 81, 10914-10923.