Table of Contents 
Molecular Biology International
Volume 2012, Article ID 614120, 11 pages
http://dx.doi.org/10.1155/2012/614120
Review Article

Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency

Gillian M. Schiralli Lester and Andrew J. Henderson

Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA

Received 15 February 2012; Accepted 9 April 2012

Academic Editor: Suryaram Gummuluru

Copyright © 2012 Gillian M. Schiralli Lester and Andrew J. Henderson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. G. Deeks, T. Wrin, T. Liegler et al., “Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia,” The New England Journal of Medicine, vol. 344, no. 7, pp. 472–480, 2001. View at Publisher · View at Google Scholar · View at Scopus
  2. A. Noë, J. Plum, and C. Verhofstede, “The latent HIV-1 reservoir in patients undergoing HAART: an archive of pre-HAART drug resistance,” Journal of Antimicrobial Chemotherapy, vol. 55, no. 4, pp. 410–412, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. D. Persaud, T. Pierson, C. Ruff et al., “A stable latent reservoir for HIV-1 in resting CD4+ T lymphocytes in infected children,” Journal of Clinical Investigation, vol. 105, no. 7, pp. 995–1003, 2000. View at Google Scholar · View at Scopus
  4. C. T. Ruff, S. C. Ray, P. Kwon et al., “Persistence of wild-type virus and lack of temporal structure in the latent reservoir for human immunodeficiency virus type 1 in pediatric patients with extensive antiretroviral exposure,” Journal of Virology, vol. 76, no. 18, pp. 9481–9492, 2002. View at Publisher · View at Google Scholar · View at Scopus
  5. T. W. Chun, L. Carruth, D. Finzi et al., “Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection,” Nature, vol. 387, no. 6629, pp. 183–188, 1997. View at Publisher · View at Google Scholar · View at Scopus
  6. T. W. Chun, L. Stuyver, S. B. Mizell et al., “Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 24, pp. 13193–13197, 1997. View at Publisher · View at Google Scholar · View at Scopus
  7. D. Finzi, M. Hermankova, T. Pierson et al., “Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy,” Science, vol. 278, no. 5341, pp. 1295–1300, 1997. View at Publisher · View at Google Scholar · View at Scopus
  8. J. K. Wong, M. Hezareh, H. F. Günthard et al., “Recovery of replication-competent HIV despite prolonged suppression of plasma viremia,” Science, vol. 278, no. 5341, pp. 1291–1295, 1997. View at Publisher · View at Google Scholar · View at Scopus
  9. T. W. Chun and A. S. Fauci, “Latent reservoirs of HIV: obstacles to the eradication of virus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 20, pp. 10958–10961, 1999. View at Publisher · View at Google Scholar · View at Scopus
  10. T. Pierson, J. McArthur, and R. F. Siliciano, “Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy,” Annual Review of Immunology, vol. 18, pp. 665–708, 2000. View at Publisher · View at Google Scholar · View at Scopus
  11. C. C. Carter, A. Onafuwa-Nuga, L. A. McNamara et al., “HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs,” Nature Medicine, vol. 16, no. 4, pp. 446–451, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. C. M. Durand, G. Ghiaur, J. D. Siliciano et al., “HIV-1 DNA is detected in bone marrow populations containing CD4+ T cells but is not found in purified CD34+ hematopoietic progenitor cells in most patients on antiretroviral therapy,” The Journal of Infectious Diseases, vol. 205, no. 6, pp. 1014–1018, 2012. View at Google Scholar
  13. S. Emiliani, W. Fischle, M. Ott, C. Van Lint, C. A. Amella, and E. Verdin, “Mutations in the tat gene are responsible for human immunodeficiency virus type 1 postintegration latency in the U1 cell line,” Journal of Virology, vol. 72, no. 2, pp. 1666–1670, 1998. View at Google Scholar · View at Scopus
  14. S. Yukl, S. Pillai, P. Li et al., “Latently-infected CD4+ T cells are enriched for HIV-1 Tat variants with impaired transactivation activity,” Virology, vol. 387, no. 1, pp. 98–108, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. R. M. van der Sluis, G. Pollakis, M. L. van Gerven, B. Berkhout, and R. E. Jeeninga, “Latency profiles of full length HIV-1 molecular clone variants with a subtype specific promoter,” Retrovirology, vol. 8, p. 73, 2011. View at Publisher · View at Google Scholar
  16. T. M. Folks, J. Justement, A. Kinter et al., “Characterization of a promonocyte clone chronically infected with HIV and inducible by 13-phorbol-12-myristate acetate,” Journal of Immunology, vol. 140, no. 4, pp. 1117–1122, 1988. View at Google Scholar · View at Scopus
  17. G. Nabel and D. Baltimore, “An inducible transcription factor activates expression of human immunodeficiency virus in T cells,” Nature, vol. 326, no. 6114, pp. 711–713, 1987. View at Google Scholar · View at Scopus
  18. S. A. Williams, L. F. Chen, H. Kwon, C. M. Ruiz-Jarabo, E. Verdin, and W. C. Greene, “NF-κB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation,” The EMBO Journal, vol. 25, no. 1, pp. 139–149, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. A. Narayanan, K. Kehn-Hall, C. Bailey, and F. Kashanchi, “Analysis of the roles of HIV-derived microRNAs,” Expert Opinion on Biological Therapy, vol. 11, no. 1, pp. 17–29, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. R. Triboulet, B. Mari, Y. L. Lin et al., “Suppression of MicroRNA-silencing pathway by HIV-1 during virus replication,” Science, vol. 315, no. 5818, pp. 1579–1582, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Jordan, D. Bisgrove, and E. Verdin, “HIV reproducibly establishes a latent infection after acute infection of T cells in vitro,” The EMBO Journal, vol. 22, no. 8, pp. 1868–1877, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. A. Jordan, P. Defechereux, and E. Verdin, “The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation,” The EMBO Journal, vol. 20, no. 7, pp. 1726–1738, 2001. View at Publisher · View at Google Scholar · View at Scopus
  23. R. Pearson, K. K. Young, J. Hokello 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,” Journal of Virology, vol. 82, no. 24, pp. 12291–12303, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. R. F. Siliciano and W. C. Greene, “HIV latency,” Cold Spring Harbor Perspectives in Medicine, vol. 1, Article ID a007096, 2011. View at Publisher · View at Google Scholar
  25. M. Kogan and J. Rappaport, “HIV-1 accessory protein Vpr: relevance in the pathogenesis of HIV and potential for therapeutic intervention,” Retrovirology, vol. 8, article 25, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. M. D. Marsden, B. P. Burke, and J. A. Zack, “HIV latency is influenced by regions of the viral genome outside of the long terminal repeats and regulatory genes,” Virology, vol. 417, pp. 394–399, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. E. M. Kilareski, S. Shah, M. R. Nonnemacher, and B. Wigdahl, “Regulation of HIV-1 transcription in cells of the monocyte-macrophage lineage,” Retrovirology, vol. 6, article 118, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. L. A. Pereira, K. Bentley, A. Peeters, M. J. Churchill, and N. J. Deacon, “A compilation of cellular transcription factor interactions with the HIV-1 LTR promoter,” Nucleic Acids Research, vol. 28, no. 3, pp. 663–668, 2000. View at Google Scholar · View at Scopus
  29. O. Rohr, C. Marban, D. Aunis, and E. Schaeffer, “Regulation of HIV-1 gene transcription: from lymphocytes to microglial cells,” Journal of Leukocyte Biology, vol. 74, no. 5, pp. 736–749, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. Y. Li, G. Mak, and B. R. Franza Jr., “In vitro study of functional involvement of Sp1, NF-κB/Rel, and AP1 in phorbol 12-myristate 13-acetate-mediated HIV-1 long terminal repeat activation,” Journal of Biological Chemistry, vol. 269, no. 48, pp. 30616–30619, 1994. View at Google Scholar · View at Scopus
  31. B. Majello, P. De Luca, G. Hagen, G. Suske, and L. Lania, “Different members of the Sp1 multigene family exert opposite transcriptional regulation of the long terminal repeat of HIV-1,” Nucleic Acids Research, vol. 22, no. 23, pp. 4914–4921, 1994. View at Google Scholar · View at Scopus
  32. N. D. Perkins, N. L. Edwards, C. S. Duckett, A. B. Agranoff, R. M. Schmid, and G. J. Nabel, “A cooperative interaction between NF-κB and Sp1 is required for HIV-1 enhancer activation,” The EMBO Journal, vol. 12, no. 9, pp. 3551–3558, 1993. View at Google Scholar · View at Scopus
  33. F. Canonne-Hergaux, D. Aunis, and E. Schaeffer, “Interactions of the transcription factor AP-1 with the long terminal repeat of different human immunodeficiency virus type 1 strains in Jurkat, glial, and neuronal cells,” Journal of Virology, vol. 69, no. 11, pp. 6634–6642, 1995. View at Google Scholar · View at Scopus
  34. K. A. Roebuck, S. De Gu, and M. F. Kagnoff, “Activating protein-1 cooperates with phorbol ester activation signals to increase HIV-1 expression,” AIDS, vol. 10, no. 8, pp. 819–826, 1996. View at Google Scholar · View at Scopus
  35. A. J. Henderson, R. I. Connor, and K. L. Calame, “C/EBP activators are required for HIV-1 replication and proviral induction in monocytic cell lines,” Immunity, vol. 5, no. 1, pp. 91–101, 1996. View at Publisher · View at Google Scholar · View at Scopus
  36. V. M. Tesmer, A. Rajadhyaksha, J. Babin, and M. Bina, “NF-IL6-mediated transcriptional activation of the long terminal repeat of the human immunodeficiency virus type 1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 15, pp. 7298–7302, 1993. View at Google Scholar · View at Scopus
  37. A. Bosque and V. Planelles, “Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells,” Blood, vol. 113, no. 1, pp. 58–65, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. R. Q. Cron, S. R. Bartz, A. Clausell, S. J. Bort, S. J. Klebanoff, and D. B. Lewis, “NFAT1 enhances HIV-1 gene expression in primary human CD4 T cells,” Clinical Immunology, vol. 94, no. 3, pp. 179–191, 2000. View at Publisher · View at Google Scholar · View at Scopus
  39. J. F. Fortin, B. Barbeau, G. A. Robichaud, M. È. Paré, A. M. Lemieux, and M. J. Tremblay, “Regulation of nuclear factor of activated T cells by phosphotyrosyl-specific phosphatase activity: a positive effect on HIV-1 long terminal repeat-driven transcription and a possible implication of SHP-1,” Blood, vol. 97, no. 8, pp. 2390–2400, 2001. View at Publisher · View at Google Scholar · View at Scopus
  40. T. A. Lodie, M. Reiner, S. Coniglio, G. Viglianti, and M. J. Fenton, “Both PU.1 and nuclear factor-κB mediate lipopolysaccharide-induced HIV-1 long terminal repeat transcription in macrophages,” Journal of Immunology, vol. 161, no. 1, pp. 268–276, 1998. View at Google Scholar · View at Scopus
  41. C. Van Lint, J. Ghysdael, P. Paras, A. Burny, and E. Verdin, “A transcriptional regulatory element is associated with a nuclease- hypersensitive site in the pol gene of human immunodeficiency virus type 1,” Journal of Virology, vol. 68, no. 4, pp. 2632–2648, 1994. View at Google Scholar · View at Scopus
  42. D. Carroll-Anzinger, A. Kumar, V. Adarichev, F. Kashanchi, and L. Al-Harthi, “Human immunodeficiency virus-restricted replication in astrocytes and the ability of gamma interferon to modulate this restriction are regulated by a downstream effector of the Wnt signaling pathway,” Journal of Virology, vol. 81, no. 11, pp. 5864–5871, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. B. Wortman, N. Darbinian, B. E. Sawaya, K. Khalili, and S. Amini, “Evidence for regulation of long terminal repeat transcription by Wnt transcription factor TCF-4 in human astrocytic cells,” Journal of Virology, vol. 76, no. 21, pp. 11159–11165, 2002. View at Publisher · View at Google Scholar · View at Scopus
  44. J. K. Chan and W. C. Greene, “NF-κB/Rel: agonist and antagonist roles in HIV-1 latency,” Current Opinion in HIV and AIDS, vol. 6, no. 1, pp. 12–18, 2011. View at Google Scholar
  45. L. Ylisastigui, R. Kaur, H. Johnson et al., “Mitogen-activated protein kinases regulate LSF occupancy at the human immunodeficiency virus type 1 promoter,” Journal of Virology, vol. 79, no. 10, pp. 5952–5962, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. F. Romerio, M. N. Gabriel, and D. M. Margolis, “Repression of human immunodeficiency virus type 1 through the novel cooperation of human factors YY1 and LSF,” Journal of Virology, vol. 71, no. 12, pp. 9375–9382, 1997. View at Google Scholar · View at Scopus
  47. G. Jiang, A. Espeseth, D. J. Hazuda, and D. M. Margolis, “c-Myc and Sp1 contribute to proviral latency by recruiting histone deacetylase 1 to the human immunodeficiency virus type 1 promoter,” Journal of Virology, vol. 81, no. 20, pp. 10914–10923, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. V. B. Cismasiu, E. Paskaleva, S. Suman Daya, M. Canki, K. Duus, and D. Avram, “BCL11B is a general transcriptional repressor of the HIV-1 long terminal repeat in T lymphocytes through recruitment of the NuRD complex,” Virology, vol. 380, no. 2, pp. 173–181, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. C. Marban, S. Suzanne, F. Dequiedt et al., “Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing,” The EMBO Journal, vol. 26, no. 2, pp. 412–423, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. M. Tyagi and J. Karn, “CBF-1 promotes transcriptional silencing during the establishment of HIV-1 latency,” The EMBO Journal, vol. 26, no. 24, pp. 4985–4995, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. T. M. Hanley and G. A. Viglianti, “Nuclear receptor signaling inhibits HIV-1 replication in macrophages through multiple trans-repression mechanisms,” Journal of Virology, vol. 85, no. 20, pp. 10834–10850, 2011. View at Google Scholar
  52. D. J. Morrison, P. S. Pendergrast, P. Stavropoulos, S. U. Colmenares, R. Kobayashi, and N. Hernandez, “FBI-1, a factor that binds to the HIV-1 inducer of short transcripts (IST), is a POZ domain protein,” Nucleic Acids Research, vol. 27, no. 5, pp. 1251–1262, 1999. View at Publisher · View at Google Scholar · View at Scopus
  53. E. S. Lee, D. Sarma, H. Zhou, and A. J. Henderson, “CCAAT/enhancer binding proteins are not required for HIV-1 entry but regulate proviral transcription by recruiting coactivators to the long-terminal repeat in monocytic cells,” Virology, vol. 299, no. 1, pp. 20–31, 2002. View at Publisher · View at Google Scholar · View at Scopus
  54. D. M. Margolis, “Histone deacetylase inhibitors and HIV latency,” Current Opinion in HIV and AIDS, vol. 6, no. 1, pp. 25–29, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. U. Mbonye and J. Karn, “Control of HIV latency by epigenetic and non-epigenetic mechanisms,” Current HIV Research, vol. 9, no. 8, pp. 554–567, 2011. View at Google Scholar
  56. D. D. Richman, D. M. Margolis, M. Delaney, W. C. Greene, D. Hazuda, and R. J. Pomerantz, “The challenge of finding a cure for HIV infection,” Science, vol. 323, no. 5919, pp. 1304–1307, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. C. Van Lint, S. Emiliani, M. Ott, and E. Verdin, “Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation,” The EMBO Journal, vol. 15, no. 5, pp. 1112–1120, 1996. View at Google Scholar · View at Scopus
  58. M. Benkirane, R. F. Chun, H. Xiao et al., “Activation of integrated provirus requires histone acetyltransferase: p300 and P/CAF are coactivators for HIV-1 Tat,” Journal of Biological Chemistry, vol. 273, no. 38, pp. 24898–24905, 1998. View at Publisher · View at Google Scholar · View at Scopus
  59. A. Pumfery, L. Deng, A. Maddukuri et al., “Chromatin remodeling and modification during HIV-1 Tat-activated transcription,” Current HIV Research, vol. 1, no. 3, pp. 343–362, 2003. View at Google Scholar · View at Scopus
  60. D. J. Steger, A. Eberharter, S. John, P. A. Grant, and J. L. Workman, “Purified histone acetyltransferase complexes stimulate HIV-1 transcription from preassembled nucleosomal arrays,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 22, pp. 12924–12929, 1998. View at Publisher · View at Google Scholar · View at Scopus
  61. E. Agbottah, L. Deng, L. O. Dannenberg, A. Pumfery, and F. Kashanchi, “Effect of SWI/SNF chromatin remodeling complex on HIV-1 Tat activated transcription,” Retrovirology, vol. 3, article 48, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. R. Easley, L. Carpio, L. Dannenberg et al., “Transcription through the HIV-1 nucleosomes: effects of the PBAF complex in Tat activated transcription,” Virology, vol. 405, no. 2, pp. 322–333, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. T. Mahmoudi, M. Parra, R. G. J. Vries et al., “The SWI/SNF chromatin-remodeling complex is a cofactor for Tat transactivation of the HIV promoter,” Journal of Biological Chemistry, vol. 281, no. 29, pp. 19960–19968, 2006. View at Publisher · View at Google Scholar · View at Scopus
  64. C. Tréand, I. du Chéné, V. Brès et al., “Requirement for SWI/SNF chromatin-remodeling complex in Tat-mediated activation of the HIV-1 promoter,” The EMBO Journal, vol. 25, no. 8, pp. 1690–1699, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. P. L. Sheridan, T. P. Mayall, E. Verdin, and K. A. Jones, “Histone acetyltransferases regulate HIV-1 enhancer activity in vitro,” Genes and Development, vol. 11, no. 24, pp. 3327–3340, 1997. View at Google Scholar · View at Scopus
  66. E. Verdin, P. Paras Jr., and C. Van Lint, “Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation,” The EMBO Journal, vol. 12, no. 8, pp. 3249–3259, 1993. View at Google Scholar · View at Scopus
  67. A. El Kharroubi, G. Piras, R. Zensen, and M. A. Martin, “Transcriptional activation of the integrated chromatin-associated human immunodeficiency virus type 1 promoter,” Molecular and Cellular Biology, vol. 18, no. 5, pp. 2535–2544, 1998. View at Google Scholar · View at Scopus
  68. M. G. Izban and D. S. Luse, “Transcription on nucleosomal templates by RNA polymerase II in vitro: inhibition of elongation with enhancement of sequence-specific pausing,” Genes and Development, vol. 5, no. 4, pp. 683–696, 1991. View at Google Scholar · View at Scopus
  69. J. L. Workman and R. G. Roeder, “Binding of transcription factor TFIID to the major late promoter during in vitro nucleosome assembly potentiates subsequent initiation by RNA polymerase II,” Cell, vol. 51, no. 4, pp. 613–622, 1987. View at Google Scholar · View at Scopus
  70. K. S. Keedy, N. M. Archin, A. T. Gates, A. Espeseth, D. J. Hazuda, and D. M. Margolis, “A limited group of class I histone deacetylases acts to repress human immunodeficiency virus type 1 expression,” Journal of Virology, vol. 83, no. 10, pp. 4749–4756, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. I. D. Chéné, E. Basyuk, Y. L. Lin et al., “Suv39H1 and HP1γ are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency,” The EMBO Journal, vol. 26, no. 2, pp. 424–435, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. J. Friedman, W. K. Cho, C. K. Chu et al., “Epigenetic silencing of HIV-1 by the histone H3 lysine 27 methyltransferase enhancer of Zeste 2,” Journal of Virology, vol. 85, no. 17, pp. 9078–9089, 2011. View at Publisher · View at Google Scholar
  73. S. E. Kauder, A. Bosque, A. Lindqvist, V. Planelles, and E. Verdin, “Epigenetic regulation of HIV-1 latency by cytosine methylation,” Plos Pathogens, vol. 5, no. 6, Article ID e1000495, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. F. Bushman, M. Lewinski, A. Ciuffi et al., “Genome-wide analysis of retroviral DNA integration,” Nature Reviews Microbiology, vol. 3, no. 11, pp. 848–858, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. M. K. Lewinski, D. Bisgrove, P. Shinn et al., “Genome-wide analysis of chromosomal features repressing human immunodeficiency virus transcription,” Journal of Virology, vol. 79, no. 11, pp. 6610–6619, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. M. K. Lewinski, M. Yamashita, M. Emerman et al., “Retroviral DNA integration: viral and cellular determinants of target-site selection,” Plos Pathogens, vol. 2, no. 6, p. e60, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. A. R. W. Schröder, P. Shinn, H. Chen, C. Berry, J. R. Ecker, and F. Bushman, “HIV-1 integration in the human genome favors active genes and local hotspots,” Cell, vol. 110, no. 4, pp. 521–529, 2002. View at Publisher · View at Google Scholar · View at Scopus
  78. A. Duverger, J. Jones, J. May et al., “Determinants of the establishment of human immunodeficiency virus type 1 latency,” Journal of Virology, vol. 83, no. 7, pp. 3078–3093, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. Y. Han, K. Lassen, D. Monie 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,” Journal of Virology, vol. 78, no. 12, pp. 6122–6133, 2004. View at Publisher · View at Google Scholar · View at Scopus
  80. Y. Han, Y. B. Lin, W. An et al., “Orientation-dependent regulation of integrated HIV-1 expression by host gene transcriptional readthrough,” Cell Host and Microbe, vol. 4, no. 2, pp. 134–146, 2008. View at Publisher · View at Google Scholar · View at Scopus
  81. H. Liu, E. C. Dow, R. Arora et al., “Integration of human immunodeficiency virus type 1 in untreated infection occurs preferentially within genes,” Journal of Virology, vol. 80, no. 15, pp. 7765–7768, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. T. Lenasi, X. Contreras, and B. M. Peterlin, “Transcriptional interference antagonizes proviral gene expression to promote HIV latency,” Cell Host and Microbe, vol. 4, no. 2, pp. 123–133, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. K. E. Shearwin, B. P. Callen, and J. B. Egan, “Transcriptional interference—a crash course,” Trends in Genetics, vol. 21, no. 6, pp. 339–345, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. S. Adhya and M. Gottesman, “Promoter occlusion: transcription through a promoter may inhibit its activity,” Cell, vol. 29, no. 3, pp. 939–944, 1982. View at Google Scholar · View at Scopus
  85. B. P. Callen, K. E. Shearwin, and J. B. Egan, “Transcriptional interference between convergent promoters caused by elongation over the promoter,” Molecular Cell, vol. 14, no. 5, pp. 647–656, 2004. View at Publisher · View at Google Scholar · View at Scopus
  86. S. K. Eszterhas, E. E. Bouhassira, D. I. K. Martin, and S. Fiering, “Transcriptional interference by independently regulated genes occurs in any relative arrangement of the genes and is influenced by chromosomal integration position,” Molecular and Cellular Biology, vol. 22, no. 2, pp. 469–479, 2002. View at Publisher · View at Google Scholar · View at Scopus
  87. I. H. Greger, F. Demarchi, M. Giacca, and N. J. Proudfoot, “Transcriptional interference perturbs the binding of Sp1 to the HIV-1 promoter,” Nucleic Acids Research, vol. 26, no. 5, pp. 1294–1300, 1998. View at Publisher · View at Google Scholar · View at Scopus
  88. S. Petruk, Y. Sedkov, K. M. Riley et al., “Transcription of bxd noncoding RNAs promoted by trithorax represses Ubx in cis by transcriptional interference,” Cell, vol. 127, no. 6, pp. 1209–1221, 2006. View at Publisher · View at Google Scholar · View at Scopus
  89. E. Gallastegui, B. Marshall, D. Vidal et al., “Combination of biological screening in a cellular model of viral latency and virtual screening identifies novel compounds that reactivate HIV-1,” Journal of Virology, vol. 86, no. 7, pp. 3795–3808, 2012. View at Google Scholar
  90. Y. K. Kim, C. F. Bourgeois, R. Pearson et al., “Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency,” The EMBO Journal, vol. 25, no. 15, pp. 3596–3604, 2006. View at Publisher · View at Google Scholar · View at Scopus
  91. J. A. D'Alessio, K. J. Wright, and R. Tjian, “Shifting players and paradigms in cell-specific transcription,” Molecular Cell, vol. 36, no. 6, pp. 924–931, 2009. View at Publisher · View at Google Scholar · View at Scopus
  92. J. M. Espinosa, “Get back TFIIF, don't let me Gdown1,” Molecular Cell, vol. 45, pp. 3–5, 2012. View at Google Scholar
  93. M. Jishage, S. Malik, U. Wagner et al., “Transcriptional regulation by Pol II(G) involving mediator and competitive interactions of Gdown1 and TFIIF with Pol II,” Molecular Cell, vol. 45, pp. 51–63, 2012. View at Google Scholar
  94. T. Raha, S. W. Cheng, and M. R. Green, “HIV-1 Tat stimulates transcription complex assembly through recruitment of TBP in the absence of TAFs,” Plos Biology, vol. 3, no. 2, article e44, 2005. View at Google Scholar · View at Scopus
  95. M. Aida, Y. Chen, K. Nakajima, Y. Yamaguchi, T. Wada, and H. Handa, “Transcriptional pausing caused by NELF plays a dual role in regulating immediate-early expression of the junB gene,” Molecular and Cellular Biology, vol. 26, no. 16, pp. 6094–6104, 2006. View at Publisher · View at Google Scholar · View at Scopus
  96. M. B. Feinberg, D. Baltimore, and A. D. Frankel, “The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 9, pp. 4045–4049, 1991. View at Google Scholar · View at Scopus
  97. S. Y. Kao, A. F. Calman, P. A. Luciw, and B. M. Peterlin, “Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product,” Nature, vol. 330, no. 6147, pp. 489–493, 1987. View at Google Scholar · View at Scopus
  98. M. F. Laspia, A. P. Rice, and M. B. Mathews, “HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation,” Cell, vol. 59, no. 2, pp. 283–292, 1989. View at Google Scholar · View at Scopus
  99. J. Lis, “Promoter-associated pausing in promoter architecture and postinitiation transcriptional regulation,” Cold Spring Harbor Symposia on Quantitative Biology, vol. 63, pp. 347–356, 1998. View at Google Scholar · View at Scopus
  100. R. Landick, “The regulatory roles and mechanism of transcriptional pausing,” Biochemical Society Transactions, vol. 34, no. 6, pp. 1062–1066, 2006. View at Publisher · View at Google Scholar · View at Scopus
  101. M. G. Guenther, S. S. Levine, L. A. Boyer, R. Jaenisch, and R. A. Young, “A chromatin landmark and transcription initiation at most promoters in human cells,” Cell, vol. 130, no. 1, pp. 77–88, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. T. H. Kim, L. O. Barrera, M. Zheng et al., “A high-resolution map of active promoters in the human genome,” Nature, vol. 436, no. 7052, pp. 876–880, 2005. View at Publisher · View at Google Scholar · View at Scopus
  103. G. W. Muse, D. A. Gilchrist, S. Nechaev et al., “RNA polymerase is poised for activation across the genome,” Nature Genetics, vol. 39, no. 12, pp. 1507–1511, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. J. Zeitlinger, A. Stark, M. Kellis et al., “RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo,” Nature Genetics, vol. 39, no. 12, pp. 1512–1516, 2007. View at Publisher · View at Google Scholar · View at Scopus
  105. L. J. Core and J. T. Lis, “Transcription regulation through promoter-proximal pausing of RNA polymerase II,” Science, vol. 319, no. 5871, pp. 1791–1792, 2008. View at Publisher · View at Google Scholar · View at Scopus
  106. T. Yamada, Y. Yamaguchi, N. Inukai, S. Okamoto, T. Mura, and H. Handa, “P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for processive transcription elongation,” Molecular Cell, vol. 21, no. 2, pp. 227–237, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. Y. Yamaguchi, N. Inukai, T. Narita, T. Wada, and H. Handa, “Evidence that negative elongation factor represses transcription elongation through binding to a DRB sensitivity-inducing factor/RNA polymerase II complex and RNA,” Molecular and Cellular Biology, vol. 22, no. 9, pp. 2918–2927, 2002. View at Publisher · View at Google Scholar · View at Scopus
  108. B. M. Peterlin and D. H. Price, “Controlling the elongation phase of transcription with P-TEFb,” Molecular Cell, vol. 23, no. 3, pp. 297–305, 2006. View at Publisher · View at Google Scholar · View at Scopus
  109. Y. H. Ping, C. Y. Chu, H. Cao, J. M. Jacque, M. Stevenson, and T. M. Rana, “Modulating HIV-1 replication by RNA interference directed against human transcription elongation factor SPT5,” Retrovirology, vol. 1, article 46, 2004. View at Publisher · View at Google Scholar · View at Scopus
  110. Y. H. Ping and T. M. Rana, “DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and DSIF during transcription elongation,” Journal of Biological Chemistry, vol. 276, no. 16, pp. 12951–12958, 2001. View at Publisher · View at Google Scholar · View at Scopus
  111. T. Wada, T. Takagi, Y. Yamaguchi et al., “DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs,” Genes and Development, vol. 12, no. 3, pp. 343–356, 1998. View at Google Scholar · View at Scopus
  112. Y. Yamaguchi, T. Takagi, T. Wada et al., “NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation,” Cell, vol. 97, no. 1, pp. 41–51, 1999. View at Google Scholar · View at Scopus
  113. K. Fujinaga, D. Irwin, Y. Huang, R. Taube, T. Kurosu, and B. M. Peterlin, “Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element,” Molecular and Cellular Biology, vol. 24, no. 2, pp. 787–795, 2004. View at Publisher · View at Google Scholar · View at Scopus
  114. C. H. Wu, Y. Yamaguchi, L. R. Benjamin et al., “NELF and DSIF cause promoter proximal pausing on the hsp70 promoter in Drosophila,” Genes and Development, vol. 17, no. 11, pp. 1402–1414, 2003. View at Google Scholar · View at Scopus
  115. V. Bres, S. M. Yoh, K. A. Jones et al., “The multi-tasking P-TEFb complex,” Current Opinion in Cell Biology, vol. 20, pp. 334–340, 2008. View at Google Scholar
  116. N. He and Q. Zhou, “New insights into the control of HIV-1 transcription: When tat meets the 7SK snRNP and super elongation complex (SEC),” Journal of Neuroimmune Pharmacology, vol. 6, no. 2, pp. 260–268, 2011. View at Publisher · View at Google Scholar · View at Scopus
  117. Q. Zhou and J. H. N. Yik, “The Yin and Yang of P-TEFb regulation: implications for human immunodeficiency virus gene expression and global control of cell growth and differentiation,” Microbiology and Molecular Biology Reviews, vol. 70, no. 3, pp. 646–659, 2006. View at Publisher · View at Google Scholar · View at Scopus
  118. D. A. Bisgrove, T. Mahmoudi, P. Henklein, and E. Verdin, “Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 34, pp. 13690–13695, 2007. View at Publisher · View at Google Scholar · View at Scopus
  119. K. J. Moon, K. Mochizuki, M. Zhou, H. S. Jeong, J. N. Brady, and K. Ozato, “The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription,” Molecular Cell, vol. 19, no. 4, pp. 523–534, 2005. View at Publisher · View at Google Scholar · View at Scopus
  120. Z. Yang, J. H. N. Yik, R. Chen et al., “Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4,” Molecular Cell, vol. 19, no. 4, pp. 535–545, 2005. View at Publisher · View at Google Scholar · View at Scopus
  121. V. Brès, N. Gomes, L. Pickle, and K. A. Jones, “A human splicing factor, SKIP, associates with P-TEFb and enhances transcription elongation by HIV-1 Tat,” Genes and Development, vol. 19, no. 10, pp. 1211–1226, 2005. View at Publisher · View at Google Scholar · View at Scopus
  122. V. Brès, T. Yoshida, L. Pickle, and K. A. Jones, “SKIP interacts with c-Myc and Menin to promote HIV-1 Tat transactivation,” Molecular Cell, vol. 36, no. 1, pp. 75–87, 2009. View at Publisher · View at Google Scholar · View at Scopus
  123. N. He, C. K. Chan, B. Sobhian et al., “Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin,” Proceedings of the National Academy of Sciences of the United State, vol. 108, pp. E636–E645, 2011. View at Google Scholar
  124. B. Sobhian, N. Laguette, A. Yatim et al., “HIV-1 Tat assembles a multifunctional transcription eongation complex and stably associates with the 7SK snRNP,” Molecular Cell, vol. 38, no. 3, pp. 439–451, 2010. View at Publisher · View at Google Scholar · View at Scopus
  125. T. Ammosova, K. Washington, Z. Debebe, J. Brady, and S. Nekhai, “Dephosphorylation of CDK9 by protein phosphatase 2A and protein phosphatase-I in Tat-activated HIV-I transcription,” Retrovirology, vol. 2, article 47, 2005. View at Publisher · View at Google Scholar · View at Scopus
  126. R. Chen, M. Liu, H. Li et al., “PP2B and PP1α cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling,” Genes and Development, vol. 22, no. 10, pp. 1356–1368, 2008. View at Publisher · View at Google Scholar · View at Scopus
  127. N. Epie, T. Ammosova, W. Turner, and S. Nekhai, “Inhibition of PP2A by LIS1 increases HIV-1 gene expression,” Retrovirology, vol. 3, article 65, 2006. View at Publisher · View at Google Scholar · View at Scopus
  128. S. Nekhai, M. Jerebtsova, A. Jackson, and W. Southerland, “Regulation of HIV-1 transcription by protein phosphatase 1,” Current HIV Research, vol. 5, no. 1, pp. 3–9, 2007. View at Publisher · View at Google Scholar · View at Scopus
  129. Y. Wang, E. C. Dow, Y. Y. Liang et al., “Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop,” Journal of Biological Chemistry, vol. 283, no. 48, pp. 33578–33584, 2008. View at Publisher · View at Google Scholar · View at Scopus
  130. T. L. Sung and A. P. Rice, “miR-198 inhibits HIV-1 gene expression and replication in monocytes and its mechanism of action appears to involve repression of cyclin T1,” Plos Pathogens, vol. 5, no. 1, Article ID e1000263, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. Z. Zhang, A. Klatt, D. S. Gilmour, and A. J. Henderson, “Negative elongation factor NELF represses human immunodeficiency virus transcription by pausing the RNA polymerase II complex,” Journal of Biological Chemistry, vol. 282, no. 23, pp. 16981–16988, 2007. View at Publisher · View at Google Scholar · View at Scopus
  132. J. N. Rao, L. Neumann, S. Wenzel, K. Schweimer, P. Rösch, and B. M. Wöhrl, “Structural studies on the RNA-recognition motif of NELF E, a cellular negative transcription elongation factor involved in the regulation of HIV transcription,” Biochemical Journal, vol. 400, no. 3, pp. 449–456, 2006. View at Publisher · View at Google Scholar · View at Scopus
  133. R. A. Marciniak and P. A. Sharp, “HIV-1 Tat protein promotes formation of more-processive elongation complexes,” The EMBO Journal, vol. 10, no. 13, pp. 4189–4196, 1991. View at Google Scholar · View at Scopus
  134. Y. Jiang, M. Liu, C. A. Spencer, and D. H. Price, “Involvement of transcription termination factor 2 in mitotic repression of transcription elongation,” Molecular Cell, vol. 14, no. 3, pp. 375–385, 2004. View at Publisher · View at Google Scholar · View at Scopus
  135. S. Buratowski, “Connections between mRNA 3′ end processing and transcription termination,” Current Opinion in Cell Biology, vol. 17, no. 3, pp. 257–261, 2005. View at Publisher · View at Google Scholar · View at Scopus
  136. E. Rosonina, S. Kaneko, and J. L. Manley, “Terminating the transcript: breaking up is hard to do,” Genes and Development, vol. 20, no. 9, pp. 1050–1056, 2006. View at Publisher · View at Google Scholar · View at Scopus
  137. S. West and N. J. Proudfoot, “Human Pcf11 enhances degradation of RNA polymerase II-associated nascent RNA and transcriptional termination,” Nucleic Acids Research, vol. 36, no. 3, pp. 905–914, 2008. View at Publisher · View at Google Scholar · View at Scopus
  138. C. Zhang, K. L. Zobeck, and Z. F. Burton, “Human RNA polymerase II elongation in slow motion: role of the TFIIF RAP74 α1 helix in nucleoside triphosphate-driven translocation,” Molecular and Cellular Biology, vol. 25, no. 9, pp. 3583–3595, 2005. View at Publisher · View at Google Scholar · View at Scopus
  139. Z. Zhang and D. S. Gilmour, “Pcf11 is a termination factor in Drosophila that dismantles the elongation complex by bridging the CTD of RNA polymerase II to the nascent transcript,” Molecular Cell, vol. 21, no. 1, pp. 65–74, 2006. View at Publisher · View at Google Scholar · View at Scopus
  140. Z. Zhang, A. Klatt, A. J. Henderson, and D. S. Gilmour, “Transcription termination factor Pcf11 limits the processivity of Pol II on an HIV provirus to repress gene expression,” Genes and Development, vol. 21, no. 13, pp. 1609–1614, 2007. View at Publisher · View at Google Scholar · View at Scopus
  141. P. Wei, M. E. Garber, S. M. Fang, W. H. Fischer, and K. A. Jones, “A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA,” Cell, vol. 92, no. 4, pp. 451–462, 1998. View at Publisher · View at Google Scholar · View at Scopus
  142. A. Henderson, A. Holloway, R. Reeves, and D. J. Tremethick, “Recruitment of SWI/SNF to the human immunodeficiency virus type 1 promoter,” Molecular and Cellular Biology, vol. 24, no. 1, pp. 389–397, 2004. View at Publisher · View at Google Scholar · View at Scopus
  143. M. Ott, M. Geyer, and Q. Zhou, “The control of HIV transcription: keeping RNA polymerase II on track,” Cell Host & Microbe, vol. 10, pp. 426–435, 2011. View at Google Scholar
  144. L. S. Weinberger, J. C. Burnett, J. E. Toettcher, A. P. Arkin, and D. V. Schaffer, “Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity,” Cell, vol. 122, no. 2, pp. 169–182, 2005. View at Publisher · View at Google Scholar · View at Scopus
  145. C. Hetzer, W. Dormeyer, M. Schnölzer, and M. Ott, “Decoding Tat: the biology of HIV Tat posttranslational modifications,” Microbes and Infection, vol. 7, no. 13, pp. 1364–1369, 2005. View at Publisher · View at Google Scholar · View at Scopus
  146. E. Col, C. Caron, D. Seigneurin-Berny, J. Gracia, A. Favier, and S. Khochbin, “The histone acetyltransferase, hGCN5, interacts with and acetylates the HIV transactivator, Tat,” Journal of Biological Chemistry, vol. 276, no. 30, pp. 28179–28184, 2001. View at Publisher · View at Google Scholar · View at Scopus
  147. R. E. Kiernan, C. Vanhulle, L. Schiltz et al., “HIV-1 Tat transcriptional activity is regulated by acetylation,” The EMBO Journal, vol. 18, no. 21, pp. 6106–6118, 1999. View at Publisher · View at Google Scholar · View at Scopus
  148. M. Ott, M. Schnölzer, J. Garnica et al., “Acetylation of the HIV-1 tat protein by p300 is important for its transcriptional activity,” Current Biology, vol. 9, no. 24, pp. 1489–1492, 1999. View at Publisher · View at Google Scholar · View at Scopus
  149. S. Pagans, A. Pedal, B. J. North et al., “SIRT1 regulates HIV transcription via Tat deacetylation,” Plos Biology, vol. 3, no. 2, article 41, 2005. View at Publisher · View at Google Scholar · View at Scopus
  150. N. Sakane, H. S. Kwon, S. Pagans et al., “Activation of HIV transcription by the viral Tat protein requires a demethylation step mediated by lysine-specific demethylase 1 (LSD1/KDM1),” PLoS Pathogens, vol. 7, no. 8, Article ID e1002184, 2011. View at Publisher · View at Google Scholar
  151. K. A. Clouse, D. Powell, I. Washington et al., “Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone,” Journal of Immunology, vol. 142, no. 2, pp. 431–438, 1989. View at Google Scholar · View at Scopus
  152. D. G. Brooks, P. A. Arlen, L. Gao, C. M. R. Kitchen, and J. A. Zack, “Identification of T cell-signaling pathways that stimulate latent HIV in primary cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 22, pp. 12955–12960, 2003. View at Publisher · View at Google Scholar · View at Scopus
  153. H. C. Yang, S. Xing, L. Shan et al., “Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation,” Journal of Clinical Investigation, vol. 119, no. 11, pp. 3473–3486, 2009. View at Publisher · View at Google Scholar · View at Scopus
  154. V. Planelles, F. Wolschendorf, and O. Kutsch, “Facts and fiction: cellular models for high throughput screening for HIV-1 reactivating drugs,” Current HIV Research, vol. 9, no. 8, pp. 568–578, 2011. View at Google Scholar
  155. D. Demonté, V. Quivy, Y. Colette, and C. Van Lint, “Administration of HDAC inhibitors to reactivate HIV-1 expression in latent cellular reservoirs: Implications for the development of therapeutic strategies,” Biochemical Pharmacology, vol. 68, no. 6, pp. 1231–1238, 2004. View at Publisher · View at Google Scholar · View at Scopus
  156. G. Lehrman, I. B. Hogue, S. Palmer et al., “Depletion of latent HIV-1 infection in vivo: a proof-of-concept study,” The Lancet, vol. 366, no. 9485, pp. 549–555, 2005. View at Publisher · View at Google Scholar · View at Scopus
  157. J. P. Routy, “Valproic acid: a potential role in treating latent HIV infection,” The Lancet, vol. 366, no. 9485, pp. 523–524, 2005. View at Publisher · View at Google Scholar · View at Scopus
  158. L. Ylisastigui, N. M. Archin, G. Lehrman, R. J. Bosch, and D. M. Margolis, “Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression,” AIDS, vol. 18, no. 8, pp. 1101–1108, 2004. View at Publisher · View at Google Scholar · View at Scopus
  159. N. M. Archin, M. Cheema, D. Parker et al., “Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection,” Plos ONE, vol. 5, no. 2, Article ID e9390, 2010. View at Publisher · View at Google Scholar · View at Scopus
  160. N. M. Archin, J. J. Eron, S. Palmer et al., “Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells,” AIDS, vol. 22, no. 10, pp. 1131–1135, 2008. View at Publisher · View at Google Scholar · View at Scopus
  161. N. Sagot-Lerolle, A. Lamine, M. L. Chaix et al., “Prolonged valproic acid treatment does not reduce the size of latent HIV reservoir,” AIDS, vol. 22, no. 10, pp. 1125–1129, 2008. View at Publisher · View at Google Scholar · View at Scopus
  162. J. D. Siliciano, J. Lai, M. Callender et al., “Stability of the latent reservoir for HIV-1 in patients receiving valproic acid,” Journal of Infectious Diseases, vol. 195, no. 6, pp. 833–836, 2007. View at Publisher · View at Google Scholar · View at Scopus
  163. A. Steel, S. Clark, I. Teo et al., “No change to HIV-1 latency with valproate therapy,” AIDS, vol. 20, no. 12, pp. 1681–1682, 2006. View at Publisher · View at Google Scholar · View at Scopus
  164. N. M. Archin, K. S. Keedy, A. Espeseth, H. Dang, D. J. Hazuda, and D. M. Margolis, “Expression of latent human immunodeficiency type 1 is induced by novel and selective histone deacetylase inhibitors,” AIDS, vol. 23, no. 14, pp. 1799–1806, 2009. View at Publisher · View at Google Scholar · View at Scopus
  165. X. Contreras, M. Schweneker, C. S. Chen et al., “Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells,” Journal of Biological Chemistry, vol. 284, no. 11, pp. 6782–6789, 2009. View at Publisher · View at Google Scholar · View at Scopus
  166. W. Bernhard, K. Barreto, A. Saunders, M. S. Dahabieh, P. Johnson, and I. Sadowski, “The Suv39H1 methyltransferase inhibitor chaetocin causes induction of integrated HIV-1 without producing a T cell response,” FEBS Letters, vol. 585, no. 22, pp. 3549–3554, 2011. View at Google Scholar