Reactivation of latent HIV: Do all roads go through P-TEFb?

Future Virology

Volumn 8, Issue 7, 2013, Pages 649-659

  Budhiraja, Sona ^a   Rice, Andrew P ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

BET inhibitors; HDAC inhibitors; JQ1; latency; NF B; P TEFb; resting CD4+ T cells; SAHA; viral reactivation

Indexed keywords

ANTIRETROVIRUS AGENT; CHEMOKINE RECEPTOR CXCR4; HISTONE DEACETYLASE INHIBITOR; HISTONE H3; HISTONE H4; POSITIVE TRANSCRIPTION ELONGATION FACTOR B; PROTEIN KINASE C INHIBITOR; TRANSACTIVATOR PROTEIN; VALPROIC ACID; VORINOSTAT;

CD4+ T LYMPHOCYTE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; TRANSCRIPTION REGULATION; VIRUS LATENCY; VIRUS REACTIVATION;

EID: 84879759440     PISSN: 17460794     EISSN: 17460808     Source Type: Journal    
DOI: 10.2217/fvl.13.52     Document Type: Review

References (76)

1. Arhel N, Kirchhoff F. Host proteins involved in HIV infection: new therapeutic targets. Biochim. Biophys. Acta 1802(3), 313-321 (2010).
2. Dorr P, Westby M, Dobbs S et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob. Agents Chemother. 49(11), 4721-4732 (2005).
3. Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 356(9239), 1423-1430 (2000).
4. Chun TW, Finzi D, Margolick J, Chadwick K, Schwartz D, Siliciano RF. In vivo fate of HIV-1-infected T cells: quantitative analysis of the transition to stable latency. Nat. Med. 1(12), 1284-1290 (1995).
5. Chomont N, El-Far M, Ancuta P et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat. Med. 15(8), 893-900 (2009).
6. Chun TW, Carruth L, Finzi D et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387(6629), 183-188 (1997).
7. Siliciano RF, Greene WC. HIV latency. Cold Spring Harb. Perspect. Med. 1(1), a007096 (2011).
8. Davey RT Jr, Bhat N, Yoder C 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. USA 96(26), 15109-15114 (1999).
9. Planelles V, Wolschendorf F, Kutsch O. Facts and fiction: cellular models for high throughput screening for HIV-1 reactivating drugs. Curr. HIV Res. 9(8), 568-578 (2011).
10. Siliciano R. Detection of latently infected cells. Presented at: Strategies for an HIV Cure. Washington, DC, USA, 28-30 November 2012.
11. Siliciano R. HIV-1 eradication strategies: design, assessment, and clinical consequences, Presented at: 20th Conference on Retroviruses and Opportunistic Infections. Atlanta, GA, USA, 3-6 March 2013.
12. Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. The challenge of finding a cure for HIV infection. Science 323(5919), 1304-1307 (2009).
13. Van Praag RM, Prins JM, Roos MT et al. 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(3), 218-226 (2001).
14. Karn J, Stoltzfus CM. Transcriptional and posttranscriptional regulation of HIV-1 gene expression. Cold Spring Harb. Perspect. Med. 2(2), a006916 (2012).
15. Archin NM, Liberty AL, Kashuba AD et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487(7408), 482-485 (2012).
16. Loetscher P, Moser B, Baggiolini M. Chemokines and their receptors in lymphocyte traffic and HIV infection. Adv. Immunol. 74, 127-180 (2000).
17. Stevenson M. HIV-1 pathogenesis. Nat. Med. 9(7), 853-860 (2003).
18. Bukrinsky MI, Sharova N, Dempsey MP et al. Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc. Natl Acad. Sci. USA 89(14), 6580-6584 (1992).
19. Coiras M, Lopez-Huertas MR, Perez-Olmeda M, Alcami J. Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs. Nat. Rev. Microbiol. 7(11), 798-812 (2009).
20. Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, Chen IS. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell 61(2), 213-222 (1990).
21. Gao WY, Cara A, Gallo RC, Lori F. Low levels of deoxynucleotides in peripheral blood lymphocytes: a strategy to inhibit human immunodeficiency virus type 1 replication. Proc. Natl Acad. Sci. USA 90(19), 8925-8928 (1993).
22. Chiu YL, Soros VB, Kreisberg JF, Stopak K, Yonemoto W, Greene WC. Cellular APOBEC3G restricts HIV-1 infection in resting CD4+ T cells. Nature 435(7038), 108-114 (2005).
23. Zhou Y, Zhang H, Siliciano JD, Siliciano RF. Kinetics of human immunodeficiency virus type 1 decay following entry into resting CD4+ T cells. J. Virol. 79(4), 2199-2210 (2005).
24. Pierson TC, Zhou Y, Kieffer TL, Ruff CT, Buck C, Siliciano RF. Molecular characterization of preintegration latency in human immunodeficiency virus type 1 infection. J. Virol. 76(17), 8518-8531 (2002).
25. Colin L, Van Lint C. Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies. Retrovirology 6, 111 (2009).
26. Keedy KS, Archin NM, Gates AT, Espeseth A, Hazuda DJ, Margolis DM. A limited group of class I histone deacetylases acts to repress human immunodeficiency virus type 1 expression. J. Virol. 83(10), 4749-4756 (2009).
27. Archin NM, Keedy KS, Espeseth A, Dang H, Hazuda DJ, Margolis DM. Expression of latent human immunodeficiency type 1 is induced by novel and selective histone deacetylase inhibitors. AIDS 23(14), 1799-1806 (2009).
28. Jenuwein T, Allis CD. Translating the histone code. Science 293(5532), 1074-1080 (2001).
29. Verdin E. DNase I-hypersensitive sites are associated with both long terminal repeats and with the intragenic enhancer of integrated human immunodeficiency virus type 1. J. Virol. 65(12), 6790-6799 (1991).
30. Karn J. The molecular biology of HIV latency: breaking and restoring the Tat-dependent transcriptional circuit. Curr. Opin. HIV AIDS 6(1), 4-11 (2011).
31. Peterlin BM, Price DH. Controlling the elongation phase of transcription with P-TEFb. Mol. Cell 23(3), 297-305 (2006).
32. He N, Liu M, Hsu J et al. HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Mol. Cell 38(3), 428-438 (2010).
33. Sobhian B, Laguette N, Yatim A et al. HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP. Mol. Cell 38(3), 439-451 (2010).
34. Rice AP, Herrmann CH. Regulation of TAK/P-TEFb in CD4+ T lymphocytes and macrophages. Curr. HIV Res. 1(4), 395-404 (2003).
35. Chiang K, Rice AP. MicroRNA-mediated restriction of HIV-1 in resting CD4+ T cells and monocytes. Viruses 4(9), 1390-1409 (2012).
36. Chiang K, Sung TL, Rice AP. Regulation of cyclin T1 and HIV-1 replication by MicroRNAsin resting CD4+ T lymphocytes. J. Virol. 86(6), 3244-3252 (2012).
37. Ramakrishnan R, Dow EC, Rice AP. Characterization of CDK9 T-loop phosphorylation in resting and activated CD4+ T lymphocytes. J. Leukoc. Biol. 86(6), 1345-1350 (2009).
38. Budhiraja S, Ramakrishnan R, Rice AP. Phosphatase PPM1A negatively regulates P-TEFb function in resting CD4+ T cells and inhibits HIV-1 gene expression. Retrovirology 9, 52 (2012).
39. Larochelle S, Amat R, Glover-Cutter K et al. Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II. Nat. Struct. Mol. Biol. 19(11), 1108-1115 (2012).
40. Budhiraja S, Famiglietti M, Bosque A, Planelles V, Rice AP. Cyclin T1 and CDK9 T-loop phosphorylation are downregulated during establishment of HIV-1 latency in primary resting memory CD4+ T cells. J. Virol. 87(2), 1211-1220 (2013).
41. Florence B, Faller DV. You bet-cha: a novel family of transcriptional regulators. Front. Biosci. 6, D1008-D1018 (2001).
42. Dey A, Chitsaz F, Abbasi A, Misteli T, Ozato K. The double bromodomain protein BRD4 binds to acetylated chromatin during interphase and mitosis. Proc. Natl Acad. Sci. USA 100(15), 8758-8763 (2003).
43. Jang MK, Mochizuki K, Zhou M, Jeong HS, Brady JN, Ozato K. The bromodomain protein BRD4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol. Cell 19(4), 523-534 (2005).
44. Yang Z, He N, Zhou Q. BRD4 recruits P-TEFb to chromosomes at late mitosis to promote G1 gene expression and cell cycle progression. Mol. Cell Biol. 28(3), 967-976 (2008).
45. Yang Z, Zhu Q, Luo K, Zhou Q. The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414(6861), 317-322 (2001).
46. Nguyen VT, Kiss T, Michels AA, Bensaude O. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414(6861), 322-325 (2001).
47. Peterlin BM, Brogie JE, Price DH. 7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic transcription. Wiley Interdiscip. Rev. RNA 3(1), 92-103 (2012).
48. Yang Z, Yik JH, Chen R et al. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein BRD4. Mol. Cell 19(4), 535-545 (2005).
49. Haaland RE, Herrmann CH, Rice AP. Increased association of 7SK snRNA with tat cofactor P-TEFb following activation of peripheral blood lymphocytes. AIDS 17(17), 2429-2436 (2003).
50. Sung TL, Rice AP. Effects of prostratin on Cyclin T1/P-TEFb function and the gene expression profile in primary resting CD4+ T cells. Retrovirology 3, 66 (2006).
51. Shirakawa K, Chavez L, Hakre S, Calvanese V, Verdin E. Reactivation of latent HIV by histone deacetylase inhibitors. Trends Microbiol. 21(6), 277-285 (2013).
52. Lehrman G, Hogue IB, Palmer S et al. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet 366(9485), 549-555 (2005).
53. Routy JP, Tremblay CL, Angel JB 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. 13(5), 291-296 (2012).
54. Archin NM, Cheema M, Parker D et al. Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection. PLoS ONE 5(2), e9390 (2010).
55. Sagot-Lerolle N, Lamine A, Chaix ML et al. Prolonged valproic acid treatment does not reduce the size of latent HIV reservoir. AIDS 22(10), 1125-1129 (2008).
56. Contreras X, Schweneker M, Chen CS et al. Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells. J. Biol. Chem. 284(11), 6782-6789 (2009).
57. Bartholomeeusen K, Fujinaga K, Xiang Y, Peterlin BM. HDAC inhibitors that release positive transcription elongation factor B (P-TEFb) from its inhibitory complex also activate HIV transcription. J. Biol. Chem. 288(20), 14400-14407 (2013).
58. Reuse S, Calao M, Kabeya K et al. Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection. PLoS ONE 4(6), e6093 (2009).
59. 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 25(2), 207-212 (2009).
60. Banerjee C, Archin N, Michaels D et al. BET bromodomain inhibition as a novel strategy for reactivation of HIV-1. J. Leukoc. Biol. 92(6), 1147-1154 (2012).
61. Bartholomeeusen K, Xiang Y, Fujinaga K, Peterlin BM. Bromodomain and extra-terminal (BET) bromodomain inhibition activate transcription via transient release of positive transcription elongation factor B (P-TEFb) from 7SK small nuclear ribonucleoprotein. J. Biol. Chem. 287(43), 36609-36616 (2012).
62. Boehm D, Calvanese V, Dar RD et al. BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism. Cell Cycle 12(3), 452-462 (2013).
63. Zhu J, Gaiha GD, John SP et al. Reactivation of latent HIV-1 by inhibition of BRD4. Cell Rep. 2(4), 807-816 (2012).
64. Filippakopoulos P, Qi J, Picaud S et al. Selective inhibition of BET bromodomains. Nature 468(7327), 1067-1073 (2010).
65. Bisgrove DA, Mahmoudi T, Henklein P, Verdin E. Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription. Proc. Natl Acad. Sci. USA 104(34), 13690-13695 (2007).
66. Malim MH, Bieniasz PD. HIV restriction factors and mechanisms of evasion. Cold Spring Harb. Perspect. Med. 2(5), a006940 (2012).
67. 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. 41(1), 277-287 (2013).
68. Contreras X, Barboric M, Lenasi T, Peterlin BM. Hmba releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activates HIV transcription. PLoS Pathog. 3(10), 1459-1469 (2007).
69. Chen R, Liu M, Li H et al. PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling. Genes Dev. 22(10), 1356-1368 (2008).
70. Barboric M, Nissen RM, Kanazawa S, Jabrane-Ferrat N, Peterlin BM. NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. Mol. Cell 8(2), 327-337 (2001).
71. Williams SA, Chen LF, Kwon H et al. prostratin antagonizes HIV latency by activating NF-kappaB. J. Biol. Chem. 279(40), 42008-42017 (2004).
72. Barboric M, Yik JH, Czudnochowski N et al. Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription. Nucleic Acids Res. 35(6), 2003-2012 (2007).
73. Beliakova-Bethell N, Zhang JX, Singhania A et al. Suberoylanilide hydroxamic acid induces limited changes in the transcriptome of primary CD4+ T cells. AIDS 27(1), 29-37 (2013).
74. Crazzolara R, Johrer K, Johnstone RW et al. Histone deacetylase inhibitors potently repress CXCR4 chemokine receptor expression and function in acute lymphoblastic leukaemia. Br. J. Haematol. 119(4), 965-969 (2002).
75. Matalon S, Palmer BE, Nold MF 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. 54(1), 1-9 (2010).
76. Shan L, Deng K, Shroff NS et al. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 36(3)