Combination of biological screening in a cellular model of viral latency and virtual screening identifies novel compounds that reactivate hiv-1

Journal of Virology

Volumn 86, Issue 7, 2012, Pages 3795-3808

  Gallastegui, Edurne ^a   Marshall, Brett ^b   Vidal, David ^c   Sanchez Duffhues, Gonzalo ^d   Collado, Juan A ^d   Alvarez Fernández, Carmen ^e   Luque, Neus ^a   Terme, Jean Michel ^a   Gatell, Josep M ^e   Sánchez Palomino, Sonsoles ^e   Muñoz, Eduardo ^d   Mestres, Jordi ^c   Verdin, Eric ^b   Jordan, Albert ^a  

^a INSTITUT DE BIOLOGIA MOLECULAR DE BARCELONA   (Spain)

^b GLADSTONE INSTITUTE OF VIROLOGY AND IMMUNOLOGY   (United States)

^c UNIVERSITAT POMPEU FABRA   (Spain)

^d UNIVERSITY OF CÓRDOBA   (Spain)

^e UNIVERSITY OF BARCELONA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

8 METHOXY 6 METHYLQUINOLIN 4 OL; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; QUINOLINE DERIVATIVE; STRESS ACTIVATED PROTEIN KINASE; T LYMPHOCYTE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ARTICLE; CELL CYCLE PROGRESSION; CELL PROLIFERATION; CONTROLLED STUDY; ENZYME ACTIVATION; FLOW CYTOMETRY; GEL ELECTROPHORESIS; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IN VITRO STUDY; LATENT PERIOD; LONG TERMINAL REPEAT; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN LOCALIZATION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TRANSCRIPTION INITIATION SITE; VIRUS INFECTIVITY; VIRUS REACTIVATION;

CD4-POSITIVE T-LYMPHOCYTES; CELL PROLIFERATION; DRUG EVALUATION, PRECLINICAL; HIV INFECTIONS; HIV-1; HUMANS; SMALL MOLECULE LIBRARIES; VIRUS ACTIVATION; VIRUS LATENCY;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84861323695     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.05972-11     Document Type: Article

References (84)

1. Archin NM, et al. 2009. Expression of latent HIV induced by the potent HDAC inhibitor suberoylanilide hydroxamic acid. AIDS Res. Hum. Retrovir. 25:207-212.
2. Areias FM, et al. 2010. In silico directed chemical probing of the adenosine receptor family. Bioorg. Med. Chem. 18:3043-3052.
3. Bisgrove D, Lewinski M, Bushman F, Verdin E. 2005. Molecular mechanisms of HIV-1 proviral latency. Expert Rev. Anti Infect. Ther. 3:805- 814.
4. Bisgrove DA, Mahmoudi T, Henklein P, Verdin E. 2007. Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription. Proc. Natl. Acad. Sci. U. S. A. 104:13690 -13695.
5. Blazkova J, et al. 2009. CpG methylation controls reactivation of HIV from latency. PLoS Pathog. 5:e1000554.
6. Bosque A, Planelles V. 2009. Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells. Blood 113:58-65.
7. Brooks DG, Arlen PA, Gao L, Kitchen CM, Zack JA. 2003. Identification of T cell-signaling pathways that stimulate latent HIV in primary cells. Proc. Natl. Acad. Sci. U. S. A. 100:12955-12960.
8. Brooks DG, et al. 2003. Molecular characterization, reactivation, and depletion of latent HIV. Immunity 19:413- 423.
9. Brooks DG, Kitchen SG, Kitchen CM, Scripture-Adams DD, Zack JA. 2001. Generation of HIV latency during thymopoiesis. Nat. Med. 7:459- 464.
10. Burke B, et al. 2007. Primary cell model for activation-inducible human immunodeficiency virus. J. Virol. 81:7424 -7434.
11. Chan JK, Greene WC. 2011. NF-kappaB/Rel: agonist and antagonist roles in HIV-1 latency. Curr. Opin. HIV AIDS 6:12-18.
12. Choi BS, et al. 2010. Novel histone deacetylase inhibitors CG05 and CG06 effectively reactivate latently infected HIV-1. AIDS 24:609-611.
13. Chun TW, et al. 1997. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387:183-188.
14. Chun TW, Engel D, Mizell SB, Ehler LA, Fauci AS. 1998. Induction of HIV-1 replication in latently infected CD4+ T cells using a combination of cytokines. J. Exp. Med. 188:83-91.
15. Chun TW, et al. 1999. Effect of interleukin-2 on the pool of latently infected, resting CD4+T cells in HIV-1-infected patients receiving highly active anti-retroviral therapy. Nat. Med. 5:651- 655.
16. Chun TW, Fauci AS. 1999. Latent reservoirs of HIV: obstacles to the eradication of virus. Proc. Natl. Acad. Sci. U. S. A. 96:10958 -10961.
17. Coiras M, Lopez-Huertas MR, Perez-Olmeda M, Alcami J. 2009. Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs. Nat. Rev. Microbiol. 7:798-812.
18. Colin L, Van Lint C. 2009. Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies. Retrovirology 6:111.
19. Contreras X, Barboric M, Lenasi T, Peterlin BM. 2007. HMBA releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activates HIV transcription. PLoS Pathog. 3:1459 -1469.
20. Contreras X, et al. 2009. Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells. J. Biol. Chem. 284:6782- 6789.
21. Daoubi M, et al. 2007. Isolation of new phenylacetylingol derivatives that reactivate HIV-1 latency and a novel spirotriterpenoid from Euphorbia officinarum latex. Bioorg. Med. Chem. 15:4577- 4584.
22. De Marco A, et al. 2008. Intragenic transcriptional cis-activation of the human immunodeficiency virus 1 does not result in allele-specific inhibition of the endogenous gene. Retrovirology 5:98.
23. Dieudonne M, et al. 2009. Transcriptional competence of the integrated HIV-1 provirus at the nuclear periphery. EMBO J. 28:2231-2243.
24. du Chene I, et al. 2007. Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and postintegration latency. EMBO J. 26:424-435.
25. Ekins S, Mestres J, Testa B. 2007. In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. Br. J. Pharmacol. 152:9 -20.
26. Emiliani S, et al. 1998. Mutations in the tat gene are responsible for human immunodeficiency virus type 1 postintegration latency in the U1 cell line. J. Virol. 72:1666 -1670.
27. Emiliani S, et al. 1996. A point mutation in the HIV-1 Tat responsive element is associated with postintegration latency. Proc. Natl. Acad. Sci. U. S. A. 93:6377- 6381.
28. Finzi D, et al. 1999. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat. Med. 5:512-517.
29. Fraser C, et al. 2000. Reduction of the HIV-1-infected T-cell reservoir by immune activation treatment is dose-dependent and restricted by the potency of antiretroviral drugs. AIDS 14:659-669.
30. Friedman J, et al. 2011. Epigenetic silencing of HIV-1 by the histone H3 lysine 27 methyltransferase enhancer of Zeste 2. J. Virol. 85:9078 -9089.
31. Gallastegui E, Millan-Zambrano G, Terme JM, Chavez S, Jordan A. 2011. Chromatin reassembly factors are involved in transcriptional interference promoting HIV latency. J. Virol. 85:3187-3202.
32. Gloire G, Legrand-Poels S, Piette J. 2006. NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem. Pharmacol. 72:1493- 1505.
33. Greger IH, Demarchi F, Giacca M, Proudfoot NJ. 1998. Transcriptional interference perturbs the binding of Sp1 to the HIV-1 promoter. Nucleic Acids Res. 26:1294 -1301.
34. Gregori-Puigjane E, Mestres J. 2006. SHED: Shannon entropy descriptors from topological feature distributions. J. Chem. Infect. Model. 46: 1615-1622.
35. Han Y, et al. 2004. Resting CD4+T cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals carry integrated HIV-1 genomes within actively transcribed host genes. J. Virol. 78:6122- 6133.
36. Hofmann TG, et al. 2001. CD95-induced JNK activation signals are transmitted by the death-inducing signaling complex (DISC), but not by Daxx. Int. J. Cancer 93:185-191.
37. Imai K, Togami H, Okamoto T. 2010. Involvement of histone H3 lysine 9 (H3K9) methyltransferase G9a in the maintenance of HIV-1 latency and its reactivation by BIX01294. J. Biol. Chem. 285:16538 -16545.
38. 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.
39. Jordan A, Defechereux P, Verdin E. 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.
40. Karn J. 1999. Tackling Tat. J. Mol. Biol. 293:235-254.
41. Kauder SE, Bosque A, Lindqvist A, Planelles V, Verdin E. 2009. Epigenetic regulation of HIV-1 latency by cytosine methylation. PLoS Pathog. 5:e1000495.
42. Kim YK, Mbonye U, Hokello J, Karn J. 2011. T-cell receptor signaling enhances transcriptional elongation from latent HIV proviruses by activating P-TEFb through an ERK-dependent pathway. J. Mol. Biol. 410: 896-916.
43. Kulkosky J, et al. 2004. Expression of latent HAART-persistent HIV type 1 induced by novel cellular activating agents. AIDS Res. Hum. Retrovir. 20:497-505.
44. Kumar S, et al. 1996. Activation of the HIV-1 long terminal repeat by cytokines and environmental stress requires an active CSBP/p38 MAP kinase. J. Biol. Chem. 271:30864 -30869.
45. Lassen K, Han Y, Zhou Y, Siliciano J, Siliciano RF. 2004. The multifactorial nature of HIV-1 latency. Trends Mol. Med. 10:525-531.
46. Lehrman G, et al. 2005. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet 366:549 -555.
47. Lehrman G, Ylisastigui L, Bosch RJ, Margolis DM. 2004. Interleukin-7 induces HIV type 1 outgrowth from peripheral resting CD4+ T cells. J. Acquir. Immune Defic. Syndr. 36:1103-1104.
48. Lenasi T, Contreras X, Peterlin BM. 2008. Transcriptional interference antagonizes proviral gene expression to promote HIV latency. Cell Host Microbe 4:123-133.
49. Lewinski MK, et al. 2005. Genome-wide analysis of chromosomal features repressing human immunodeficiency virus transcription. J. Virol. 79:6610-6619.
50. Lusic M, Marcello A, Cereseto A, Giacca M. 2003. Regulation of HIV-1 gene expression by histone acetylation and factor recruitment at the LTR promoter. EMBO J. 22:6550-6561.
51. Marini A, Harper JM, Romerio F. 2008. An in vitro system to model the establishment and reactivation of HIV-1 latency. J. Immunol. 181:7713- 7720.
52. Marquez N, et al. 2008. Differential effects of phorbol-13-monoesters on human immunodeficiency virus reactivation. Biochem. Pharmacol. 75: 1370-1380.
53. Matalon S, et al. 2010. The histone deacetylase inhibitor ITF2357 decreases surface CXCR4 and CCR5 expression on CD4(+) T-cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro. J. Acquir. Immune Defic. Syndr. 54:1-9.
54. Medina-Ramirez M, et al. 2011. Broadly cross-neutralizing antibodies in HIV-1 patients with undetectable viremia. J. Virol. 85:5804 -5813.
55. Micheva-Viteva S, et al. 2011. High-throughput screening uncovers a compound that activates latent HIV-1 and acts cooperatively with a histone deacetylase (HDAC) inhibitor. J. Biol. Chem. 286:21083-21091.
56. Paulsen M, et al. 2011. Modulation of CD4+ T-cell activation by CD95 co-stimulation. Cell Death Differ. 18:619-631.
57. Perez M, et al. 2010. Bryostatin-1 synergizes with histone deacetylase inhibitors to reactivate HIV-1 from latency. Curr. HIV. Res. 8:418-429.
58. Peterlin BM, Price DH. 2006. Controlling the elongation phase of transcription with P-TEFb. Mol. Cell 23:297-305.
59. Pion M, et al. 2003. Transcriptional suppression of in vitro-integrated human immunodeficiency virus type 1 does not correlate with proviral DNA methylation. J. Virol. 77:4025- 4032.
60. Poli G, Kinter AL, Fauci AS. 1994. Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected U1 cells: inhibition of inductive effects by the interleukin 1 receptor antagonist. Proc. Natl. Acad. Sci. U. S. A. 91:108 -112.
61. Quivy V, De Walque S, Van Lint C. 2007. Chromatin-associated regulation of HIV-1 transcription: implications for the development of therapeutic strategies. Subcell. Biochem. 41:371-396.
62. Reuse S, et al. 2009. Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection. PLoS One 4:e6093.
63. Richards J, et al. 1999. Phase I evaluation of humanized OKT3: toxicity and immunomodulatory effects of hOKT3gamma4. Cancer Res. 59: 2096-2101.
64. Sadowski I, Lourenco P, Malcolm T. 2008. Factors controlling chromatin organization and nucleosome positioning for establishment and maintenance of HIV latency. Curr. HIV Res. 6:286 -295.
65. Sagot-Lerolle N, et al. 2008. Prolonged valproic acid treatment does not reduce the size of latent HIV reservoir. AIDS 22:1125-1129.
66. Savarino A, et al. 2009. " Shock and kill" effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence. Retrovirology 6:52.
67. Schreck R, Rieber P, Baeuerle PA. 1991. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J. 10:2247-2258.
68. Shehu-Xhilaga M, et al. 2009. The novel histone deacetylase inhibitors metacept-1 and metacept-3 potently increase HIV-1 transcription in latently infected cells. AIDS 23:2047-2050.
69. Siliciano JD, et al. 2007. Stability of the latent reservoir for HIV-1 in patients receiving valproic acid. J. Infect. Dis. 195:833- 836.
70. Stanley SK, Folks TM, Fauci AS. 1989. Induction of expression of human immunodeficiency virus in a chronically infected promonocytic cell line by ultraviolet irradiation. AIDS Res. Hum. Retrovir. 5:375-384.
71. Swiggard WJ, et al. 2005. Human immunodeficiency virus type 1 can establish latent infection in resting CD4_T cells in the absence of activating stimuli. J. Virol. 79:14179 -14188.
72. Trono D, et al. 2010. HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science 329:174 -180.
73. Tyagi M, Pearson RJ, 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.
74. 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.
75. Verdin E, Paras P, Jr., Van Lint C. 1993. Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation. EMBO J. 12:3249 -3259.
76. Vicenzi E, Poli G. 1994. Ultraviolet irradiation and cytokines as regulators of HIV latency and expression. Chem. Biol. Interact. 91:101-109.
77. Vidal D, Garcia-Serna R, Mestres J. 2011. Ligand-based approaches to in silico pharmacology. Methods Mol. Biol. 672:489 -502.
78. Wang FX, et al. 2005. IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART. J. Clin. Investig. 115:128 -137.
79. Williams SA, et al. 2004. Prostratin antagonizes HIV latency by activating NF-kappaB. J. Biol. Chem. 279:42008-42017.
80. Williams SA, et al. 2006. NF-kappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J. 25:139 -149.
81. Williams SA, Kwon H, Chen LF, Greene WC. 2007. Sustained induction of NF-kappa B is required for efficient expression of latent human immunodeficiency virus type 1. J. Virol. 81:6043- 6056.
82. Yang HC, et al. 2009. Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation. J. Clin. Investig. 119:3473-3486.
83. Ying H, Zhang Y, Lin S, Han Y, Zhu HZ. 2010. Histone deacetylase inhibitor Scriptaid reactivates latent HIV-1 promoter by inducing histone modification in in vitro latency cell lines. Int. J. Mol. Med. 26:265-272.
84. Ylisastigui L, Archin NM, Lehrman G, Bosch RJ, Margolis DM. 2004. Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression. AIDS 18:1101-1108.