Epigenetic control of HIV-1 post integration latency: Implications for therapy

Clinical Epigenetics

Volumn 7, Issue 1, 2015, Pages

  Kumar, Amit ^a   Darcis, Gilles ^b   Van Lint, Carine ^b   Herbein, Georges ^a  

^a Hôpital Saint Jacques ^*  (France)

^b UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

Author keywords

CD4+ T cells; Epigenetics; Histone modifications; HIV 1; Latency; Microglia; MicroRNAs; Monocyte macrophage

Indexed keywords

HISTONE DEACETYLASE INHIBITOR; METHYLTRANSFERASE INHIBITOR; MICRORNA; VIRUS DNA;

CD4+ T LYMPHOCYTE; CYTOPATHOGENIC EFFECT; DNA METHYLATION; EPIGENETICS; GENETIC REGULATION; HISTONE METHYLATION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNE RESPONSE; MACROPHAGE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN PROCESSING; REVIEW; VIRAL GENETICS; VIRUS DNA CELL DNA INTERACTION; VIRUS EXPRESSION; VIRUS GENOME; VIRUS LATENCY; VIRUS REACTIVATION;

EID: 84942162776     PISSN: 18687075     EISSN: 18687083     Source Type: Journal    
DOI: 10.1186/s13148-015-0137-6     Document Type: Review

References (150)

1. Palmer S. Advances in detection and monitoring of plasma viremia in HIVinfected individuals receiving antiretroviral therapy. Curr Opin HIV AIDS. 2013;8(2):87-92.
2. Van Lint C, Bouchat S, Marcello A. HIV-1 transcription and latency: an update. Retrovirology. 2013;10:67.
3. Kim SH, Gerver SM, Fidler S, Ward H. Adherence to antiretroviral therapy in adolescents living with HIV: systematic review and meta-analysis. AIDS. 2014;28(13):1945-56.
4. Global update on HIV treatment 2013: Web page link: http://apps.who.int/iris/bitstream/10665/85326/1/9789241505734_eng.pdf. Accessed 10 September 2015.
5. Archin NM, Margolis DM. Emerging strategies to deplete the HIV reservoir. Curr Opin Infect Dis. 2014;27(1):29-35.
6. Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011;1(1):a007096.
7. Siliciano JD, Siliciano RF. HIV-1 eradication strategies: design and assessment. Curr Opin HIV AIDS. 2013;8(4):318-25.
8. Xing S, Siliciano RF. Targeting HIV latency: pharmacologic strategies toward eradication. Drug Discov Today. 2013;18(11-12):541-51.
9. Abbas W, Tariq M, Iqbal M, Kumar A, Herbein G. Eradication of HIV-1 from the macrophage reservoir: an uncertain goal? Viruses. 2015;7(4):1578-98.
10. Kumar A, Abbas W, Herbein G. HIV-1 latency in monocytes/macrophages. Viruses. 2014;6(4):1837-60.
11. Kumar A, Herbein G. The macrophage: a therapeutic target in HIV-1 infection. Mol Cell Ther. 2014,2:10.
12. McKinstry KK, Strutt TM, Swain SL. The potential of CD4 T-cell memory. Immunology. 2010;130(1):1-9.
13. Gras G, Kaul M. Molecular mechanisms of neuroinvasion by monocytesmacrophages in HIV-1 infection. Retrovirology. 2010;7:30.
14. Garrido C, Margolis DM. Translational challenges in targeting latent HIV infection and the CNS reservoir problem. J Neurovirol. 2015;21(3):222-6.
15. Cosenza MA, Zhao ML, Si Q, Lee SC. Human brain parenchymal microglia express CD14 and CD45 and are productively infected by HIV-1 in HIV-1 encephalitis. Brain Pathol. 2002;12(4):442-55.
16. Gray LR, Roche M, Flynn JK, Wesselingh SL, Gorry PR, Churchill MJ. Is the central nervous system a reservoir of HIV-1? Curr Opin HIV AIDS. 2014;9(6):552-8.
17. Churchill MJ, Wesselingh SL, Cowley D, Pardo CA, McArthur JC, Brew BJ, et al. Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia. Ann Neurol. 2009;66(2):253-8.
18. Talal AH, Monard S, Vesanen M, Zheng Z, Hurley A, Cao Y, et al. Virologic and immunologic effect of antiretroviral therapy on HIV-1 in gut-associated lymphoid tissue. J Acquir Immune Defic Syndr. 2001;26(1):1-7.
19. Poles MA, Boscardin WJ, Elliott J, Taing P, Fuerst MM, McGowan I, et al. Lack of decay of HIV-1 in gut-associated lymphoid tissue reservoirs in maximally suppressed individuals. J Acquir Immune Defic Syndr. 2006;43(1):65-8.
20. Chun TW, Nickle DC, Justement JS, Meyers JH, Roby G, Hallahan CW, et al. Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis. 2008;197(5):714-20.
21. Yukl SA, Gianella S, Sinclair E, Epling L, Li Q, Duan L, et al. Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy. J Infect Dis. 2010;202(10):1553-61.
22. Yukl SA, Shergill AK, Ho T, Killian M, Girling V, Epling L, et al. The distribution of HIV DNA and RNA in cell subsets differs in gut and blood of HIV-positive patients on ART: implications for viral persistence. J Infect Dis. 2013;208(8):1212-20.
23. Rothenberger MK, Keele BF, Wietgrefe SW, Fletcher CV, Beilman GJ, Chipman JG, et al. Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption. Proc Natl Acad Sci U S A. 2015;112(10):E1126-34.
24. Smith PD, Meng G, Salazar-Gonzalez JF, Shaw GM. Macrophage HIV-1 infection and the gastrointestinal tract reservoir. J Leukoc Biol. 2003;74(5):642-9.
25. Shen R, Meng G, Ochsenbauer C, Clapham PR, Grams J, Novak L, et al. Stromal down-regulation of macrophage CD4/CCR5 expression and NF-κB activation mediates HIV-1 non-permissiveness in intestinal macrophages. PLoS Pathog. 2011;7(5):e1002060.
26. Eriksson S, Graf EH, Dahl V, Strain MC, Yukl SA, Lysenko ES, et al. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLoS Pathog. 2013;9(2):e1003174.
27. Siliciano JM, Siliciano RF. The remarkable stability of the latent reservoir for HIV-1 in resting memory CD4+ T cells. J Infect Dis, 2015, pii: jiv219 [Epub ahead of print].
28. Le Douce V, Herbein G, Rohr O, Schwartz C. Molecular mechanisms of HIV-1 persistence in the monocyte-macrophage lineage. Retrovirology. 2010;7:32.
29. Colin L, Van Lint C. Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies. Retrovirology. 2009;6:111.
30. Mbonye U, Karn J. Control of HIV latency by epigenetic and non-epigenetic mechanisms. Curr HIV Res. 2011;9(8):554-67.
31. Schneider M, Tigges B, Meggendorfer M, Helfer M, Ziegenhain C, Brack-Werner R. A new model for post-integration latency in macroglial cells to study HIV-1 reservoirs of the brain. AIDS. 2015;29(10):1147-59.
32. Schröder AR, Shinn P, Chen H, Berry C, Ecker JR, Bushman F. HIV-1 integration in the human genome favors active genes and local hotspots. Cell. 2002;110(4):521-9.
33. Rezaei SD, Cameron PU. Human immunodeficiency virus (HIV)-1 integration sites in viral latency. Curr HIV AIDS Rep. 2015;12(1):88-96.
34. Han Y, Lassen K, Monie D, Sedaghat AR, Shimoji S, Liu X, et al. 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. 2004;78(12):6122-33.
35. Barr SD, Ciuffi A, Leipzig J, Shinn P, Ecker JR, Bushman FD. HIV integration site selection: targeting in macrophages and the effects of different routes of viral entry. Mol Ther. 2006;14(2):218-25.
36. Ciuffi A, Llano M, Poeschla E, Hoffmann C, Leipzig J, Shinn P, et al. A role for LEDGF/p75 in targeting HIV DNA integration. Nat Med. 2005;11(12):1287-9.
37. Shun MC, Raghavendra NK, Vandegraaff N, Daigle JE, Hughes S, Kellam P, et al. LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration. Genes Dev. 2007;21(14):1767-78.
38. Lelek M, Casartelli N, Pellin D, Rizzi E, Souque P, Severgnini M, et al. Chromatin organization at the nuclear pore favours HIV replication. Nat Commun. 2015;6:6483.
39. Desimmie BA, Weydert C, Schrijvers R, Vets S, Demeulemeester J, Proost P, et al. HIV-1 IN/Pol recruits LEDGF/p75 into viral particles. Retrovirology. 2015;12:16.
40. Ocwieja KE, Brady TL, Ronen K, Huegel A, Roth SL, Schaller T, et al. HIV integration targeting: a pathway involving transportin-3 and the nuclear pore protein RanBP2. PLoS Pathog. 2011;7(3):e1001313.
41. Marini B, Kertesz-Farkas A, Ali H, Lucic B, Lisek K, Manganaro L, et al. Nuclear architecture dictates HIV-1 integration site selection. Nature. 2015;521(7551):227-31.
42. Shearwin KE, Callen BP, Egan JB. Transcriptional interference—a crash course. Trends Genet. 2005;21(6):339-45.
43. Han Y, Lin YB, An W, Xu J, Yang HC, O’Connell K, et al. Orientationdependent regulation of integrated HIV-1 expression by host gene transcriptional read through. Cell Host Microbe. 2008;4(2):134-46.
44. Lenasi T, Contreras X, Peterlin BM. Transcriptional interference antagonizes proviral gene expression to promote HIV latency. Cell Host Microbe. 2008;4(2):123-33.
45. Shan L, Yang HC, Rabi SA, Bravo HC, Shroff NS, Irizarry RA, et al. Influence of host gene transcription level and orientation on HIV-1 latency in a primarycell model. J Virol. 2011;85(11):5384-93.
46. Gallastegui E, Millán-Zambrano G, Terme JM, Chávez S, Jordan A. Chromatin reassembly factors are involved in transcriptional interference promoting HIV latency. J Virol. 2011;85(7):3187-202.
47. Verdin E, Paras Jr P, Van Lint C. Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation. EMBO J. 1993;12(8):3249-59.
48. Rohr O, Marban C, Aunis D, Schaeffer E. Regulation of HIV-1 gene transcription: from lymphocytes to microglial cells. J Leukoc Biol. 2003;74(5):736-49.
49. Van Lint C, Emiliani S, Ott M, Verdin E. Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation. EMBO J. 1996;15(5):1112-20.
50. Lusic M, Giacca M. Regulation of HIV-1 latency by chromatin structure and nuclear architecture. J Mol Biol. 2015;427(3):688-94.
51. Lusic M, Marcello A, Cereseto A, Giacca M. Regulation of HIV-1 gene expression by histone acetylation and factor recruitment at the LTR promoter. EMBO J. 2003;22(24):6550-61.
52. Tripathy MK, Abbas W, Herbein G. Epigenetic regulation of HIV-1 transcription. Epigenomics. 2011;3(4):487-502.
53. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J. 2003;370(Pt 3):737-49.
54. Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M. Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov. 2012;11(5):384-400.
55. Williams SA, Chen LF, Kwon H, Ruiz-Jarabo CM, Verdin E, Greene WC. NFkappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J. 2006;25(1):139-49.
56. Marban C, Redel L, Suzanne S, Van Lint C, Lecestre D, Chasserot-Golaz S, et al. COUP-TF interacting protein 2 represses the initial phase of HIV-1 gene transcription in human microglial cells. Nucleic Acids Res. 2005;33(7):2318-31.
57. Marban C, Suzanne S, Dequiedt F, de Walque S, Redel L, Van Lint C, et al. Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing. EMBO J. 2007;26(2):412-23.
58. Reuse S, Calao M, Kabeya K, Guiguen A, Gatot JS, Quivy V, et al. Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection. PLoS One. 2009;4(6):e6093.
59. Huber K, Doyon G, Plaks J, Fyne E, Mellors JW, Sluis-Cremer N. Inhibitors of histone deacetylases: correlation between isoform specificity and reactivation of HIV type 1 (HIV-1) from latently infected cells. J Biol Chem. 2011;286(25):22211-8.
60. Margolis DM. Histone deacetylase inhibitors and HIV latency. Curr Opin HIV AIDS. 2011;6(1):25-9.
61. Palmisano I, Della Chiara G, D’Ambrosio RL, Huichalaf C, Brambilla P, Corbetta S, et al. Amino acid starvation induces reactivation of silenced transgenes and latent HIV-1 provirus via down-regulation of histone deacetylase 4 (HDAC4). Proc Natl Acad Sci U S A. 2012;109(34):E2284-93.
62. du Chéné I, Basyuk E, Lin YL, Triboulet R, Knezevich A, Chable-Bessia C, et al. Suv39H1 and HP1 gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency. EMBO J. 2007;26(2):424-35.
63. Pearson R, Kim YK, Hokello J, Lassen K, Friedman J, Tyagi M, et al. Epigenetic silencing of human immunodeficiency virus (HIV) transcription by formation of restrictive chromatin structures at the viral long terminal repeat drives the progressive entry of HIV into latency. J Virol. 2008;82(24):12291-303.
64. Imai K, Togami H, Okamoto T. Involvement of histone H3 lysine 9 (H3K9) methyltransferase G9a in the maintenance of HIV-1 latency and its reactivation by BIX01294. J Biol Chem. 2010;285(22):16538-45.
65. Friedman J, Cho WK, Chu CK, Keedy KS, Archin NM, Margolis DM, et al. Epigenetic silencing of HIV-1 by the histone H3 lysine 27 methyltransferase enhancer of Zeste 2. J Virol. 2011;85(17):9078-89.
66. Li E, Zhang Y. DNA methylation in mammals. Cold Spring Harb Perspect Biol. 2014;6(5):a019133.
67. Kauder SE, Bosque A, Lindqvist A, Planelles V, Verdin E. Epigenetic regulation of HIV-1 latency by cytosine methylation. PLoS Pathog. 2009;5(6):e1000495.
68. Blazkova J, Trejbalova K, Gondois-Rey F, Halfon P, Philibert P, Guiguen A, et al. CpG methylation controls reactivation of HIV from latency. PLoS Pathog. 2009;5(8):e1000554.
69. Maricato JT, Furtado MN, Takenaka MC, Nunes ER, Fincatti P, Meliso FM, et al. Epigenetic modulations in activated cells early after HIV-1 infection and their possible functional consequences. PLoS One. 2015;10(4):e0119234.
70. Blazkova J, Murray D, Justement JS, Funk EK, Nelson AK, Moir S, et al. Paucity of HIV DNA methylation in latently infected, resting CD4+ T cells from infected individuals receiving antiretroviral therapy. J Virol. 2012;86(9):5390-2.
71. Lf C, Fischle W, Verdin E, Greene WC. Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science. 2001;293(5535):1653-7.
72. Chen LF, Mu Y, Greene WC. Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-κB. EMBO J. 2002;21(23):6539-48.
73. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004;23(12):2369-80.
74. Pagans S, Pedal A, North BJ, Kaehlcke K, Marshall BL, Dorr A, et al. SIRT1 regulates HIV transcription via Tat deacetylation. PLoS Biol. 2005;3(2):e41.
75. Kwon HS, Brent MM, Getachew R, Jayakumar P, Chen LF, Schnolzer M, et al. Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivation. Cell Host Microbe. 2008;3(3):158-67.
76. Nebbioso A, Carafa V, Benedetti R, Altucci L. Trials with “epigenetic” drugs: an update. Mol Oncol. 2012;6(6):657-82.
77. Héninger E, Krueger TE, Lang JM. Augmenting antitumor immune responses with epigenetic modifying agents. Front Immunol. 2015;6:29.
78. Deeks SG. HIV: shock and kill. Nature. 2012;487(7408):439-40.
79. Paris M, Porcelloni M, Binaschi M, Fattori D. Histone deacetylase inhibitors: from bench to clinic. J Med Chem. 2008;51(6):1505-29.
80. Bose P, Dai Y, Grant S. Histone deacetylase inhibitor (HDACI) mechanisms of action: emerging insights. Pharmacol Ther. 2014;143(3):323-36.
81. Archin NM, Espeseth A, Parker D, Cheema M, Hazuda D, Margolis DM. Expression of latent HIV induced by the potent HDAC inhibitor suberoylanilide hydroxamic acid. AIDS Res Hum Retroviruses. 2009;25(2):207-12.
82. Savarino A, Mai A, Norelli S, El Daker S, Valente S, Rotili D, et al. “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. 2009;6:52.
83. Barton KM, Archin NM, Keedy KS, Espeseth AS, Zhang YL, Gale J, et al. Selective HDAC inhibition for the disruption of latent HIV-1 infection. PLoS One. 2014;9(8):e102684.
84. Rasmussen TA, Schmeltz Søgaard O, Brinkmann C, Wightman F, Lewin SR, Melchjorsen J, et al. Comparison of HDAC inhibitors in clinical development: effect on HIV production in latently infected cells and T-cell activation. Hum Vaccin Immunother. 2013;9(5):993-1001.
85. Contreras X, Schweneker M, Chen CS, McCune JM, Deeks SG, Martin J, et al. Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells. J Biol Chem. 2009;284(11):6782-9.
86. Archin NM, Sung JM, Garrido C, Soriano-Sarabia N, Margolis DM. Eradicating HIV-1 infection: seeking to clear a persistent pathogen. Nat Rev Microbiol. 2014;12(11):750-64.
87. Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature. 2012;487(7408):482-5.
88. Olesen R, Vigano S, Rasmussen T, Søgaard OS, Ouyang Z, Buzon M, et al. Innate immune activity correlates with CD4 T cell-associated HIV-1 DNA decline during latency-reversing treatment with panobinostat. J Virol. 2015.
89. Elliott JH, Wightman F, Solomon A, Ghneim K, Ahlers J, Cameron MJ, et al. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog. 2014;10(10):e1004473.
90. Bullen CK, Laird GM, Durand CM, Siliciano JD, Siliciano RF. New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo. Nat Med. 2014;20(4):425-9.
91. Jønsson KL, Tolstrup M, Vad-Nielsen J, Kjær K, Laustsen A, Andersen MN, et al. Histone deacetylase inhibitor romidepsin inhibits de novo HIV-1 infections. Antimicrob Agents Chemother. 2015;59(7):3984-94.
92. Bernhard W, Barreto K, Saunders A, Dahabieh MS, Johnson P, Sadowski I. The Suv39H1 methyltransferase inhibitor chaetocin causes induction of integrated HIV-1 without producing a T cell response. FEBS Lett. 2011;585(22):3549-54.
93. Bouchat S, Gatot JS, Kabeya K, Cardona C, Colin L, Herbein G, et al. Histone methyltransferase inhibitors induce HIV-1 recovery in resting CD4(+) T cells from HIV-1-infected HAART-treated patients. AIDS. 2012;26(12):1473-82.
94. Tripathy MK, McManamy ME, Burch BD, Archin NM, Margolis DM. H3K27 demethylation at the proviral promoter sensitizes latent HIV to the effects of vorinostat in ex-vivo cultures of resting CD4+ T cells. J Virol. 2015;89(16):8392-405.
95. Foulks JM, Parnell KM, Nix RN, Chau S, Swierczek K, Saunders M, et al. Epigenetic drug discovery: targeting DNA methyltransferases. J Biomol Screen. 2012;17(1):2-17.
96. McGovern AP, Powell BE, Chevassut TJ. A dynamic multi-compartmental model of DNA methylation with demonstrable predictive value in hematological malignancies. J Theor Biol. 2012;310:14-20.
97. Fernandez G, Zeichner SL. Cell line-dependent variability in HIV activation employing DNMT inhibitors. Virol J. 2010;7:266.
98. Davey Jr RT, Bhat N, Yoder C, Chun TW, Metcalf JA, Dewar R, et al. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S A. 1999;96(26):15109-14.
99. Vandergeeten C, Fromentin R, DaFonseca S, Lawani MB, Sereti I, Lederman MM, et al. Interleukin-7 promotes HIV persistence during antiretroviral therapy. Blood. 2013;121(21):4321-9.
100. Jiang G, Mendes EA, Kaiser P, Sankaran-Walters S, Tang Y, Weber MG, et al. Reactivation of HIV latency by a newly modified ingenol derivative via protein kinase Cδ-NF-κB signaling. AIDS. 2014;28(11):1555-66.
101. Chauhan A. Enigma of HIV-1 latent infection in astrocytes: an in-vitro study using protein kinase C agonist as a latency reversing agent. Microbes Infect. 2015;17(9):651-9.
102. Shang HT, Ding JW, Yu SY, Wu T, Zhang QL, Liang FJ. Progress and challenges in the use of latent HIV-1 reactivating agents. Acta Pharmacol Sin. 2015;36(8):908-16.
103. Fujinaga K, Barboric M, Li Q, Luo Z, Price DH, Peterlin BM. PKC phosphorylates HEXIM1 and regulates P-TEFb activity. Nucleic Acids Res. 2012;40(18):9160-70.
104. Contreras X, Mzoughi O, Gaston F, Peterlin MB, Bahraoui E. Protein kinase C-delta regulates HIV-1 replication at an early post-entry step in macrophages. Retrovirology. 2012;9:37.
105. Wu SY, Chiang CM. The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J Biol Chem. 2007;282(18):13141-5.
106. Zhou Q, Yik JH. The Yin and Yang of P-TEFb regulation: implications for human immunodeficiency virus gene expression and global control of cell growth and differentiation. Microbiol Mol Biol Rev. 2006;70(3):646-59.
107. Bisgrove DA, Mahmoudi T, Henklein P, Verdin E. Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription. Proc Natl Acad Sci U S A. 2007;104(34):13690-5.
108. Verstraete N, Kuzmina A, Diribarne G, Nguyen VT, Kobbi L, Ludanyi M, et al. A Cyclin T1 point mutation that abolishes positive transcription elongation factor (P-TEFb) binding to Hexim1 and HIV tat. Retrovirology. 2014;11:50.
109. Banerjee C, Archin N, Michaels D, Belkina AC, Denis GV, Bradner J, et al. BET bromodomain inhibition as a novel strategy for reactivation of HIV-1. J Leukoc Biol. 2012;92(6):1147-54.
110. Li Z, Guo J, Wu Y, Zhou Q. The BET bromodomain inhibitor JQ1 activates HIV latency through antagonizing Brd4 inhibition of Tat-transactivation. Nucleic Acids Res. 2013;41(1):277-87.
111. Boehm D, Calvanese V, Dar RD, Xing S, Schroeder S, Martins L, et al. BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism. Cell Cycle. 2013;12(3):452-62.
112. Suh JJ, Pettinati HM, Kampman KM, O’Brien CP. The status of disulfiram: a half of a century later. J Clin Psychopharmacol. 2006;26(3):290-302.
113. Xing S, Bullen CK, Shroff NS, Shan L, Yang HC, Manucci JL, et al. Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation. J Virol. 2011;85(12):6060-4.
114. Doyon G, Zerbato J, Mellors JW, Sluis-Cremer N. Disulfiram reactivates latent HIV-1 expression through depletion of the phosphatase and tensin homolog. AIDS. 2013;27(2):F7-11.
115. Spivak AM, Andrade A, Eisele E, Hoh R, Bacchetti P, Bumpus NN, et al. A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy. Clin Infect Dis. 2014;58(6):883-90.
116. Detsika MG, Psarris A, Paraskevis D. MicroRNAs and HIV latency: a complex and promising relationship. AIDS Rev. 2012;14(3):188-94.
117. Kumar A, Herbein G. Epigenetic regulation of human cytomegalovirus latency: an update. Epigenomics. 2014;6(5):533-46.
118. Bennasser Y, Le SY, Yeung ML, Jeang KT. HIV-1 encoded candidate micro-RNAs and their cellular targets. Retrovirology. 2004;1:43.
119. Omoto S, Ito M, Tsutsumi Y, Ichikawa Y, Okuyama H, Brisibe EA, et al. HIV-1 nef suppression by virally encoded microRNA. Retrovirology. 2004;1:44.
120. Lamers SL, Fogel GB, McGrath MS. HIV-miR-H1 evolvability during HIV pathogenesis. Biosystem. 2010;101(2):88-96.
121. Wang X, Ye L, Hou W, Zhou Y, Wang YJ, Metzger DS, et al. Cellular microRNA expression correlates with susceptibility of monocytes/macrophages to HIV-1 infection. Blood. 2009;113(3):671-4.
122. Chang JR, Mukerjee R, Bagashev A, Del Valle L, Chabrashvili T, Hawkins BJ, et al. HIV-1 Tat protein promotes neuronal dysfunction through disruption of microRNAs. J Biol Chem. 2011;286(47):41125-34.
123. Wang L, Li G, Yao ZQ, Moorman JP, Ning S. MicroRNA regulation of viral immunity, latency, and carcinogenesis of selected tumor viruses and HIV. Rev Med Virol. 2015;25(5):320-41.
124. Schopman NC, Willemsen M, Liu YP, Bradley T, van Kampen A, Baas F, et al. Deep sequencing of virus-infected cells reveals HIV-encoded small RNAs. Nucleic Acids Res. 2012;40(1):414-27.
125. Lin J, Cullen BR. Analysis of the interaction of primate retroviruses with the human RNA interference machinery. J Virol. 2007;81(22):12218-26.
126. Klase Z, Kale P, Winograd R, Gupta MV, Heydarian M, Berro R, et al. HIV-1 TAR element is processed by Dicer to yield a viral micro-RNA involved in chromatin remodeling of the viral LTR. BMC Mol Biol. 2007;8:63.
127. Ouellet DL, Plante I, Landry P, Barat C, Janelle ME, Flamand L, et al. Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element. Nucleic Acids Res. 2008;36(7):2353-65.
128. Swaminathan G, Navas-Martín S, Martín-García J. MicroRNAs and HIV-1 infection: antiviral activities and beyond. J Mol Biol. 2014;426(6):1178-97.
129. Sung TL, Rice AP. miR-198 inhibits HIV-1 gene expression and replication in monocytes and its mechanism of action appears to involve repression of cyclin T1. PLoS Pathog. 2009;5(1):e1000263.
130. Chiang K, Sung TL, Rice AP. Regulation of cyclin T1 and HIV-1 Replication by microRNAs in resting CD4+ T lymphocytes. J Virol. 2012;86(6):3244-52.
131. Triboulet R, Mari B, Lin YL, Chable-Bessia C, Bennasser Y, Lebrigand K, et al. Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science. 2007;315(5818):1579-82.
132. Shen CJ, Jia YH, Tian RR, Ding M, Zhang C, Wang JH. Translation of Pur-α is targeted by cellular miRNAs to modulate the differentiation-dependent susceptibility of monocytes to HIV-1 infection. FASEB J. 2012;26(11):4755-64.
133. Patel P, Ansari MY, Bapat S, Thakar M, Gangakhedkar R, Jameel S. The microRNA miR-29a is associated with human immunodeficiency virus latency. Retrovirology. 2014;11:108.
134. Ruelas DS, Chan JK, Oh E, Heidersbach AJ, Hebbeler AM, Chavez L, et al. MicroRNA-155 Reinforces HIV Latency. J Biol Chem. 2015;290(22):13736-48.
135. Routy JP, Tremblay CL, Angel JB, Trottier B, Rouleau D, Baril JG, et al. Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study. HIV Med. 2012;13(5):291-6.
136. Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, Erikstrup C, Solomon A, et al. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV. 2014;1(1):e13-21.
137. Wei DG, Chiang V, Fyne E, Balakrishnan M, Barnes T, Graupe M, et al. Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells from patients on suppressive antiretroviral therapy at concentrations achieved by clinical dosing. PLoS Pathog. 2014;10(4):e1004071.
138. Wightman F, Lu HK, Solomon AE, Saleh S, Harman AN, Cunningham AL, et al. Entinostat is a histone deacetylase inhibitor selective for class 1 histone deacetylases and activates HIV production from latently infected primary T cells. AIDS. 2013;27(18):2853-62.
139. Lu HK, Gray LR, Wightman F, Ellenberg P, Khoury G, Cheng WJ, et al. Ex vivo response to histone deacetylase (HDAC) inhibitors of the HIV long terminal repeat (LTR) derived from HIV-infected patients on antiretroviral therapy. PLoS One. 2014;9(11):e113341.
140. Ying H, Zhang Y, Zhou X, Qu X, Wang P, Liu S, et al. Selective histonedeacetylase inhibitor M344 intervenes in HIV-1 latency through increasing histone acetylation and activation of NF-kappaB. PLoS One. 2012;7(11):e48832.
141. Kashanchi F, Melpolder JC, Epstein JS, Sadaie MR. Rapid and sensitive detection of cell-associated HIV-1 in latently infected cell lines and in patient cells using sodium-n-butyrate induction and RT-PCR. J Med Virol. 1997;52(2):179-89.
142. Yin H, Zhang Y, Zhou X, Zhu H. Histonedeacetylase inhibitor Oxamflatin increase HIV-1 transcription by inducing histone modification in latently infected cells. Mol Biol Rep. 2011;38(8):5071-8.
143. Ying H, Zhang Y, Lin S, Han Y, Zhu HZ. Histone deacetylase inhibitor Scriptaid reactivates latent HIV-1 promoter by inducing histone modification in in vitro latency cell lines. Int J Mol Med. 2010;26(2):265-72.
144. Matalon S, Palmer BE, Nold MF, Furlan A, Kassu A, Fossati G, et al. 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. 2010;54(1):1-9.
145. Choi BS, Lee HS, Oh YT, Hyun YL, Ro S, Kim SS, et al. Novel histone deacetylase inhibitors CG05 and CG06 effectively reactivate latently infected HIV-1. AIDS. 2010;24(4):609-11.
146. Kulkosky J, Sullivan J, Xu Y, Souder E, Hamer DH, Pomerantz RJ. Expression of latent HAART-persistent HIV type 1 induced by novel cellular activating agents. AIDS Res Hum Retroviruses. 2004;20(5):497-505.
147. Williams SA, Chen LF, Kwon H, Fenard D, Bisgrove D, Verdin E, et al. Prostratin antagonizes HIV latency by activating NF-kappaB. J Biol Chem. 2004;279(40):42008-17.
148. Warrilow D, Gardner J, Darnell GA, Suhrbier A, Harrich D. HIV type 1 inhibition by protein kinase C modulatory compounds. AIDS Res Hum Retroviruses. 2006;22(9):854-64.
149. Kovochich M, Marsden MD, Zack JA. Activation of latent HIV using drugloaded nanoparticles. PLoS One. 2011;6(4):e18270.
150. Darcis G, Kula A, Bouchat S, Fujinaga K, Corazza F, Ait-Ammar A, et al. An in-depth comparison of latency-reversing agent combinations in various in vitro and Ex vivo HIV-1 latency models identified bryostatin-1 + JQ1 and ingenol-B + JQ1 to potently reactivate viral gene expression. PLoS Pathog. 2015;11(7):e1005063.