Skip to main content

Epigenetic Regulation of HIV-1 Persistence and Evolving Strategies for Virus Eradication

  • Chapter
  • First Online:
Epigenetics: Development and Disease

Part of the book series: Subcellular Biochemistry ((SCBI,volume 61))

Abstract

Despite the intense effort put by researchers globally to understand Human Immunodeficiency Virus (HIV-1) pathogenesis since its discovery 30 years ago, the acquired knowledge till date is not good enough to eradicate HIV-1 from an infected individual. HIV-1 infects cells of the human immune system and integrates into the host cell genome thereby leading to persistent infection in these cells. Based on the activation status of the cells, the infection could be productive or result in latent infection. The current regimen used to treat HIV-1 infection in an AIDS patient includes combination of antiretroviral drugs called Highly Active Anti-Retroviral Therapy (HAART). A major challenge for the success of HAART has been these latent reservoirs of HIV which remain hidden and pose major hurdle for the eradication of virus. Combination of HAART therapy with simultaneous activation of latent reservoirs of HIV-1 seems to be the future of anti-retroviral therapy; however, this will require a much better understanding of the mechanisms and regulation of HIV-1 latency. In this chapter, we have tried to elaborate on HIV-1 latency, highlighting the strategies employed by the virus to ensure persistence in the host with specific focus on epigenetic regulation of latency. A complete understanding of HIV-1 latency will be extremely essential for ultimate eradication of HIV-1 from the human host.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aagaard L, Laible G, Selenko P, Schmid M, Dorn R, Schotta G, Kuhfittig S, Wolf A, Lebersorger A, Singh PB, Reuter G, Jenuwein T (1999) Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31. EMBO J 18:1923–1938

    Article  PubMed  CAS  Google Scholar 

  • Adhya S, Gottesman M (1982) Promoter occlusion: transcription through a promoter may inhibit its activity. Cell 29:939–944

    Article  PubMed  CAS  Google Scholar 

  • Ahmad K, Henikoff S (2002) The histone variant H33 marks active chromatin by replication-independent nucleosome assembly. Mol Cell 9:191–1200

    Article  Google Scholar 

  • Antoni BA, Rabson AB, Kinter A, Bodkin M, Poli G (1994) NF-kappa B-dependent and -independent pathways of HIV activation in a chronically infected T cell line. Virology 202:684–694

    Article  PubMed  CAS  Google Scholar 

  • Archin NM, Keedy KS, Espeseth A, Dang H, Hazuda DJ, Margolis DM (2009) Expression of latent human immunodeficiency type 1 is induced by novel and selective histone deacetylase inhibitors. AIDS 23:1799–1806

    Article  CAS  Google Scholar 

  • Asin S, Taylor JA, Trushin S, Bren G, Paya CV (1999) Ikappakappa mediates NF-kappaB activation in human immunodeficiency virus-infected cells. J Virol 73:3893–3903

    PubMed  CAS  Google Scholar 

  • Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410:120–124

    Article  PubMed  CAS  Google Scholar 

  • Benkirane M, Chun RF, Xiao H, Ogryzko VV, Howard BH, Nakatani Y, Jeang KT (1998) Activation of integrated provirus requires histone acetyltransferase p300 and P/CAF are coactivators for HIV-1 Tat. J Biol Chem 273:24898–24905

    Article  PubMed  CAS  Google Scholar 

  • Bennasser Y, Le SY, Yeung ML, Jeang KT (2004) HIV-1 encoded candidate micro-RNAs and their cellular targets. Retrovirology 1:43

    Article  PubMed  CAS  Google Scholar 

  • Bennasser Y, Yeung ML, Jeang KT (2006) HIV-1 TAR RNA subverts RNA interference in transfected cells through sequestration of TAR RNA-binding protein TRBP. J Biol Chem 281:27674–27678

    Article  PubMed  CAS  Google Scholar 

  • Berger SL (2002) Histone modifications in transcriptional regulation. Curr Opin Genet Dev 12:142–148

    Article  PubMed  CAS  Google Scholar 

  • Blankson JN, Persaud D, Siliciano RF (2002) The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med 53:557–593

    Article  PubMed  CAS  Google Scholar 

  • Blazkova J, Trejbalova K, Gondois-Rey F, Halfon P, Philibert P, Guiguen A, Verdin E, Olive D, Van Lint C, Hejnar J, Hirsch I (2009) CpG methylation controls reactivation of HIV from latency. PLoS Pathog 5:e1000554

    Article  PubMed  CAS  Google Scholar 

  • Bohnlein E, Lowenthal JW, Siekevitz M, Ballard DW, Franza BR, Greene WC (1988) The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV. Cell 53:827–836

    Article  PubMed  CAS  Google Scholar 

  • Boldogh I, Albrecht T, Porter DD (1996) Persistent viral infections. In: Baron S (ed) Medical microbiology, 4th edn. University of Texas Medical Branch, Galveston

    Google Scholar 

  • Bosque A, Planelles V (2011) Studies of HIV-1 latency in an ex vivo model that uses primary central memory T cells. Methods 53:54–61

    Article  PubMed  CAS  Google Scholar 

  • Boulanger MC, Liang C, Russell RS, Lin R, Bedford MT, Wainberg MA, Richard S (2005) Methylation of Tat by PRMT6 regulates human immunodeficiency virus type 1 gene expression. J Virol 79:124–131

    Article  PubMed  CAS  Google Scholar 

  • Bres V, Kiernan R, Emiliani S, Benkirane M (2002) Tat acetyl-acceptor lysines are important for human immunodeficiency virus type-1 replication. J Biol Chem 277:22215–22221

    Article  PubMed  CAS  Google Scholar 

  • Brooks DG, Kitchen SG, Kitchen CM, Scripture-Adams DD, Zack JA (2001) Generation of HIV latency during thymopoiesis. Nat Med 7:459–464

    Article  PubMed  CAS  Google Scholar 

  • Bukrinsky M (2006) SNFing HIV transcription. Retrovirology 3:49

    Article  PubMed  CAS  Google Scholar 

  • Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S, Stevenson M (1992) Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc Natl Acad Sci U S A 89:6580–6584

    Article  PubMed  CAS  Google Scholar 

  • Butera ST, Perez VL, Wu BY, Nabel GJ, Folks TM (1991a) Oscillation of the human immunodeficiency virus surface receptor is regulated by the state of viral activation in a CD4+ cell model of chronic infection. J Virol 65:4645–4653

    PubMed  CAS  Google Scholar 

  • Butera ST, Perez VL, Besansky NJ, Chan WC, Wu BY, Nabel GJ, Folks TM (1991b) Extrachromosomal human immunodeficiency virus type-1 DNA can initiate a spreading infection of HL-60 cells. J Cell Biochem 45:366–373

    Article  PubMed  CAS  Google Scholar 

  • Cherrier T, Suzanne S, Redel L, Calao M, Marban C, Samah B, Mukerjee R, Schwartz C, Gras G, Sawaya BE, Zeichner SL, Aunis D, Van Lint C, Rohr O (2009) p21(WAF1) gene promoter is epigenetically silenced by CTIP2 and SUV39H1. Oncogene 28:3380–3389

    Article  PubMed  CAS  Google Scholar 

  • Chiu YL, Soros VB, Kreisberg JF, Stopak K, Yonemoto W, Greene WC (2005) Cellular APOBEC3G restricts HIV-1 infection in resting CD4+ T cells. Nature 435:108–114

    Article  PubMed  CAS  Google Scholar 

  • Choudhary SK, Archin NM, Margolis DM (2008) Hexamethylbisacetamide and disruption of human immunodeficiency virus type 1 latency in CD4(+) T cells. J Infect Dis 197:1162–1170

    Article  PubMed  CAS  Google Scholar 

  • Choudhary SK, Rezk NL, Ince WL, Cheema M, Zhang L, Su L, Swanstrom R, Kashuba AD, Margolis DM (2009) Suppression of human immunodeficiency virus type 1 (HIV-1) viremia with reverse transcriptase and integrase inhibitors CD4+ T-cell recovery and viral rebound upon interruption of therapy in a new model for HIV treatment in the humanized Rag2−/−{gamma}c−/− mouse. J Virol 83:8254–8258

    Article  PubMed  CAS  Google Scholar 

  • Chugh P, Fan S, Planelles V, Maggirwar SB, Dewhurst S, Kim B (2007) Infection of human immunodeficiency virus and intracellular viral Tat protein exert a pro-survival effect in a human microglial cell line. J Mol Biol 366:67–81

    Article  PubMed  CAS  Google Scholar 

  • Chun TW, Finzi D, Margolick J, Chadwick K, Schwartz D, Siliciano RF (1995) In vivo fate of HIV-1-infected T cells: quantitative analysis of the transition to stable latency. Nat Med 1:1284–1290

    Article  PubMed  CAS  Google Scholar 

  • Chun TW, Engel D, Mizell SB, Hallahan CW, Fischette M, Park S, Davey RT Jr, Dybul M, Kovacs JA, Metcalf JA, Mican JM, Berrey MM, Corey L, Lane HC, Fauci AS (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

    Article  PubMed  CAS  Google Scholar 

  • Chun TW, Justement JS, Lempicki RA, Yang J, Dennis G Jr, Hallahan CW, Sanford C, Pandya P, Liu S, Mc Laughlin M, Ehler LA, Moir S, Fauci AS (2003) Gene expression and viral prodution in latently infected resting CD4+ T cells in viremic versus aviremic HIV-infected individuals. Proc Natl Acad Sci U S A 100:1908–1913

    Article  PubMed  CAS  Google Scholar 

  • Col E, Caron C, Seigneurin-Berny D, GraciaJ Favier A, Khochbin S (2001) The histone acetyltransferase hGCN5 interacts with and acetylates the HIV transactivator Tat. J Biol Chem 276:28179–28184

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Contreras X, Schweneker M, Chen CS, McCune JM, Deeks SG, Martin J, Peterlin BM (2009) Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells. J Biol Chem 284:6782–6789

    Article  PubMed  CAS  Google Scholar 

  • Coull JJ, Romerio F, Sun JM, Volker JL, Galvin KM, Davie JR, Shi Y, Hansen U, Margolis DM (2000) The human factors YY1 and LSF repress the human immunodeficiency virus type 1 long terminal repeat via recruitment of histone deacetylase 1. J Virol 74:6790–6799

    Article  PubMed  CAS  Google Scholar 

  • de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370:737–749

    Article  PubMed  Google Scholar 

  • Deng L, Wang D, de la Fuente C, Wang L, Li H, Lee CG, Donnelly R, Wade JD, Lambert P, Kashanchi F (2001) Enhancement of the p300 HAT activity by HIV-1 Tat on chromatin DNA. Virology 289:312–326

    Article  PubMed  CAS  Google Scholar 

  • Dorr A, Kiermer V, Pedal A, Rackwitz HR, Henklein P, Schubert U, Zhou MM, Verdin E, Ott M (2002) Transcriptional synergy between Tat and PCAF is dependent on the binding of acetylated Tat to the PCAF bromodomain. EMBO J 21:2715–2723

    Article  PubMed  CAS  Google Scholar 

  • du Chene I, Basyuk E, Lin YL, Triboulet R, Knezevich A, Chable-Bessia C, Mettling C, Baillat V, Reynes J, Corbeau P, Bertrand E, Marcello A, Emiliani S, Kiernan R, Benkirane M (2007) Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency. EMBO J 26:424–435

    Article  PubMed  CAS  Google Scholar 

  • Duh EJ, Maury WJ, Folks TM, Fauci AS, Rabson AB (1989) Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat. Proc Natl Acad Sci U S A 86:5974–5978

    Article  PubMed  CAS  Google Scholar 

  • Dutton RW, Bradley LM, Swain SL (1998) T cell memory. Annu Rev Immunol 16:201–223

    Article  PubMed  CAS  Google Scholar 

  • Efstathiou S, Preston CM (2005) Towards an understanding of the molecular basis of herpes simplex virus latency. Virus Res 111:108–119

    Article  PubMed  CAS  Google Scholar 

  • Emiliani S, Van Lint C, Fischle W, Paras P Jr, Ott M, Brady J, Verdin E (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

    Article  PubMed  CAS  Google Scholar 

  • Emiliani S, Fischle W, Ott M, Van Lint C, Amella CA, Verdin E (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

    PubMed  CAS  Google Scholar 

  • Farber DL, Acuto O, Bottomly K (1997) Differential T cell receptor-mediated signaling in naive and memory CD4 T cells. Eur J Immunol 27:2094–2101

    Article  PubMed  CAS  Google Scholar 

  • Folks TM, Justement J, Kinter A, Dinarello CA, Fauci AS (1987) Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science 238:800–802

    Article  PubMed  CAS  Google Scholar 

  • Folks TM, Clouse KA, Justement J, Rabson A, Duh E, Kehrl JH, Fauci AS (1989) Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc Natl Acad Sci U S A 86:2365–2368

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Ganesh L, Burstein E, Guha-Niyogi A, Louder MK, Mascola JR, Klomp LW, Wijmenga C, Duckett CS, Nabel GJ (2003) The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes. Nature 426:853–857

    Google Scholar 

  • Gao L, Cueto MA, Asselbergs F, Atadja P (2002) Cloning and functional characterization of HDAC11 a novel member of the human histone deacetylase family. J Biol Chem 277:25748–25755

    Article  PubMed  CAS  Google Scholar 

  • Garriga J, Peng J, Parreno M, Price DH, Henderson EE, Grana X (1998) Upregulation of cyclin T1/CDK9 complexes during T cell activation. Oncogene 17:3093–3102

    Article  PubMed  CAS  Google Scholar 

  • Geleziunas R, Xu W, Takeda K, Ichijo H, Greene WC (2001) HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell. Nature 410:834–838

    Article  PubMed  CAS  Google Scholar 

  • Giri MS, Nebozyhn M, Raymond A, Gekonge B, Hancock A, Creer S, Nicols C, Yousef M, Foulkes AS, Mounzer K, Shull J, Silvestri G, Kostman J, Collman RG, Showe L, Montaner LJ (2009) Circulating monocytes in HIV-1-infected viremic subjects exhibit an antiapoptosis gene signature and virus- and host-mediated apoptosis resistance. J Immunol 182:4459–4470

    Article  PubMed  CAS  Google Scholar 

  • Greenway AL, McPhee DA, Allen K, Johnstone R, Holloway G, Mills J, Azad A, Sankovich S, Lambert P (2002) Human immunodeficiency virus type 1 Nef binds to tumor suppressor p53 and protects cells against p53-mediated apoptosis. J Virol 76:2692–2702

    Article  PubMed  CAS  Google Scholar 

  • Grewal SI, Moazed D (2003) Heterochromatin and epigenetic control of gene expression. Science 301:798–802

    Article  PubMed  CAS  Google Scholar 

  • Guillemard E, Jacquemot C, Aillet F, Schmitt N, Barre-Sinoussi F, Israel N (2004) Human immunodeficiency virus 1 favors the persistence of infection by activating macrophages through TNF. Virology 329:371–380

    Article  PubMed  CAS  Google Scholar 

  • Haase AD, Jaskiewicz L, Zhang H, Laine S, Sack R, Gatignol A, Filipowicz W (2005) TRBP a regulator of cellular PKR and HIV-1 virus expression interacts with Dicer and functions in RNA silencing. EMBO Rep 6:961–967

    Article  PubMed  CAS  Google Scholar 

  • Han Y, Lassen K, Monie D, Sedaghat AR, Shimoji S, Liu X, Pierson TC, Margolick JB, Siliciano RF, Siliciano JD (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

    Article  PubMed  CAS  Google Scholar 

  • Hargreaves DC, Crabtree GR (2011) ATP-dependent chromatin remodeling: genetics genomics and mechanisms. Cell Res 21:396–420

    Article  PubMed  CAS  Google Scholar 

  • Hazuda DJ, Young SD, Guare JP, Anthony NJ, Gomez RP, Wai JS, Vacca JP, Handt L, Motzel SL, Klein HJ, Dornadula G, Danovich RM, Witmer MV, Wilson KA, Tussey L, Schleif WA, Gabryelski LS, Jin L, Miller MD, Casimiro DR, Emini EA, Shiver JW (2004) Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques. Science 305:528–532

    Article  PubMed  CAS  Google Scholar 

  • He LM, Hsu J, Xue Y, Chou S, Burlingame A, Krogan NJ, Alber T, Zhou Q (2010) HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Mol Cell 38:428–438

    Article  PubMed  CAS  Google Scholar 

  • Henikoff S, Furuyama T, Ahmad K (2004) Histone variants nucleosome assembly and epigenetic inheritance. Trends Genet 20:320–326

    Article  PubMed  CAS  Google Scholar 

  • Herrmann CH, Carroll RG, Wei P, Jones KA, Rice AP (1998) Tat-associated kinase TAK activity is regulated by distinct mechanisms in peripheral blood lymphocytes and promonocytic cell lines. J Virol 72:9881–9888

    PubMed  CAS  Google Scholar 

  • Hofman MJ, Higgins J, Matthews TB, Pedersen NC, Tan C, Schinazi RF, North TW (2004) Efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1. Antimicrob Agents Chemother 48:3483–3490

    Article  PubMed  CAS  Google Scholar 

  • Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H, Huang W, Squires K, Verlinghieri G, Zhang H (2007) Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat Med 13:1241–1247

    Article  PubMed  CAS  Google Scholar 

  • Imai K, Okamoto T (2006) Transcriptional repression of human immunodeficiency virus type 1 by AP-4. J Biol Chem 281:12495–12505

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Janicki SM, Tsukamoto T, Salghetti SE, Tansey WP, Sachidanandam R, Prasanth KV, Ried T, Shav-Tal Y, Bertrand E, Singer RH, Spector DL (2004) From silencing to gene expression: real-time analysis in single cells. Cell 116:683–698

    Article  PubMed  CAS  Google Scholar 

  • Jenkins MK, Khoruts A, Ingulli E, Mueller DL, McSorley SJ, Reinhardt RL, Itano A, Pape KA (2001) In vivo activation of antigen-specific CD4 T cells. Annu Rev Immunol 19:23–45

    Article  PubMed  CAS  Google Scholar 

  • Jiang G, Espeseth A, Hazuda DJ, Margolis DM (2007) c-Myc and Sp1 contribute to proviral latency by recruiting histone deacetylase 1 to the human immunodeficiency virus type 1 promoter. J Virol 81:10914–10923

    Article  PubMed  CAS  Google Scholar 

  • Jin C, Zang C, Wei G, Cui K, Peng W, Zhao K, Felsenfeld G (2009) H3.3/H2AZ double variant-containing nucleosomes mark ‘nucleosome-free regions’ of active promoters and other regulatory regions. Nat Genet 41:941–945

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Kamine J, Elangovan B, Subramanian T, Coleman D, Chinnadurai G (1996) Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator. Virology 216:357–366

    Article  PubMed  CAS  Google Scholar 

  • Kauder SE, Bosque A, Lindqvist A, Planelles V, Verdin E (2009) Epigenetic regulation of HIV-1 latency by cytosine methylation. PLoS Pathog 5:e1000495

    Article  PubMed  CAS  Google Scholar 

  • Keedy KS, Archin NM, Gates AT, Espeseth A, Hazuda DJ, Margolis DM (2009) A limited group of class I histone deacetylases acts to repress human immunodeficiency virus type 1 expression. J Virol 83:4749–4756

    Google Scholar 

  • Kiernan RE, Vanhulle C, Schiltz L, Adam E, Xiao H, Maudoux F, Calomme C, Burny A, Nakatani Y, Jeang KT, Benkirane M, Van Lint C (1999) HIV-1 tat transcriptional activity is regulated by acetylation. EMBO J 18:6106–6118

    Article  PubMed  CAS  Google Scholar 

  • Klase Z, Kale P, Winograd R, Gupta MV, Heydarian M, Berro R, McCaffrey T, Kashanchi F (2007) 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 8:63

    Article  PubMed  CAS  Google Scholar 

  • Klase Z, Winograd R, Davis J, Carpio L, Hildreth R, Heydarian M, Fu S, McCaffrey T, Meiri E, Ayash-Rashkovsky M, Gilad S, Bentwich Z, Kashanchi F (2009) HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression. Retrovirology 6:18

    Article  PubMed  CAS  Google Scholar 

  • Klichko V, Archin N, Kaur R, Lehrman G, Margolis D (2006) Hexamethylbisacetamide remodels the human immunodeficiency virus type 1 (HIV-1) promoter and induces Tat-independent HIV-1 expression but blunts cell activation. J Virol 80:4570–4579

    Article  PubMed  CAS  Google Scholar 

  • Korin YD, Zack JA (1999) Nonproductive human immunodeficiency virus type 1 infection in nucleoside-treated G0 lymphocytes. J Virol 73:6526–6532

    PubMed  CAS  Google Scholar 

  • Kulkosky J, Culnan DM, Roman J, Dornadula G, Schnell M, Boyd MR, Pomerantz RJ (2001) Prostratin: activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART. Blood 98:3006–3015

    Article  PubMed  CAS  Google Scholar 

  • Kwon H, Imbalzano AN, Khavari PA, Kingston RE, Green MR (1994) Nucleosome disruption and enhancement of activator binding by a human SW1/SNF complex. Nature 370:477–481

    Article  PubMed  CAS  Google Scholar 

  • Lehrman G, Hogue IB, Palmer S, Jennings C, Spina CA, Wiegand A, Landay AL, Coombs RW, Richman DD, Mellors JW, Coffin JM, Bosch RJ, Margolis DM (2005) Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet 366:549–555

    Article  PubMed  CAS  Google Scholar 

  • Lenasi T, Contreras X, Peterlin BM (2008) Transcriptional interference antagonizes proviral gene expression to promote HIV latency. Cell Host Microbe 4:123–133

    Article  PubMed  CAS  Google Scholar 

  • Levy DN, Refaeli Y, Weiner DB (1995) Extracellular Vpr protein increases cellular permissiveness to human immunodeficiency virus replication and reactivates virus from latency. J Virol 69:1243–1252

    PubMed  CAS  Google Scholar 

  • Lewinski MK, Yamashita M, Emerman M, Ciuffi A, Marshall H, Crawford G, Collins F, Shinn P, Leipzig J, Hannenhalli S, Berry CC, Ecker JR, Bushman FD (2006) Retroviral DNA integration: viral and cellular determinants of target-site selection. PLoS Pathog 2:e60

    Article  PubMed  CAS  Google Scholar 

  • Liu H, Dow EC, Arora R, Kimata JT, Bull LM, Arduino RC, Rice AP (2006) Integration of human immunodeficiency virus type 1 in untreated infection occurs preferentially within genes. J Virol 80:7765–7768

    Article  PubMed  CAS  Google Scholar 

  • MacNeil A, Sankale JL, Meloni ST, Sarr AD, Mboup S, Kanki P (2006) Genomic sites of human immunodeficiency virus type 2 (HIV-2) integration: similarities to HIV-1 in vitro and possible differences in vivo. J Virol 80:7316–7321

    Article  PubMed  CAS  Google Scholar 

  • Mahmoudi T, Parra M, Vries RG, Kauder SE, Verrijzer CP, Ott M, Verdin E (2006) The SWI/SNF chromatin-remodeling complex is a cofactor for Tat transactivation of the HIV promoter. J Biol Chem 281:19960–19968

    Article  PubMed  CAS  Google Scholar 

  • Maison C, Almouzni G (2004) HP1 and the dynamics of heterochromatin maintenance. Nat Rev Mol Cell Biol 5:296–304

    Article  PubMed  CAS  Google Scholar 

  • Marban C, Suzanne S, Dequiedt F, de Walque S, Redel L, Van Lint C, Aunis D, Rohr O (2007) Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing. EMBO J 26:412–423

    Article  PubMed  CAS  Google Scholar 

  • Marzio G, Tyagi M, Gutierrez MI, Giacca M (1998) HIV-1 tat transactivator recruits p300 and CREB-binding protein histone acetyltransferases to the viral promoter. Proc Natl Acad Sci U S A 95:13519–13524

    Article  PubMed  CAS  Google Scholar 

  • Matalon S, Rasmussen TA, Dinarello CA (2011) Histone deacetylase inhibitors for purging HIV-1 from the latent reservoir. Mol Med 17:466–472

    Article  PubMed  CAS  Google Scholar 

  • McElhinny JA, MacMorran WS, Bren GD, Ten RM, Israel A, Paya CV (1995) Regulation of I kappa B alpha and p105 in monocytes and macrophages persistently infected with human immunodeficiency virus. J Virol 69:1500–1509

    PubMed  CAS  Google Scholar 

  • Meyerhans A, Vartanian JP, Hultgren C, Plikat U, Karlsson A, Wang L, Eriksson S, Wain-Hobson S (1994) Restriction and enhancement of human immunodeficiency virus type 1 replication by modulation of intracellular deoxynucleoside triphosphate pools. J Virol 68:535–540

    PubMed  CAS  Google Scholar 

  • Nabel G, Baltimore D (1987) An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature 326:711–713

    Article  PubMed  CAS  Google Scholar 

  • Nathans R, Chu CY, Serquina AK, Lu CC, Cao H, Rana TM (2009) Cellular microRNA and P bodies modulate host-HIV-1 interactions. Mol Cell 34:696–709

    Article  PubMed  CAS  Google Scholar 

  • Niederman TM, Thielan BJ, Ratner L (1989) Human immunodeficiency virus type 1 negative factor is a transcriptional silencer. Proc Natl Acad Sci U S A 86:1128–1132

    Article  PubMed  CAS  Google Scholar 

  • North BJ, Verdin E (2004) Sirtuins: Sir2-related NAD-dependent protein deacetylases. Genome Biol 5:224

    Article  PubMed  Google Scholar 

  • O’Brien SK, Cao H, Nathans R, Ali A, Rana TM (2010) P-TEFb kinase complex phosphorylates histone H1 to regulate expression of cellular and HIV-1 genes. J Biol Chem 285:29713–29720

    Article  PubMed  Google Scholar 

  • Ott M, Schnolzer M, Garnica J, Fischle W, Emiliani S, Rackwitz HR, Verdin E (1999) Acetylation of the HIV-1 Tat protein by p300 is important for its transcriptional activity. Curr Biol 9:1489–1492

    Article  PubMed  CAS  Google Scholar 

  • Ouellet DL, Plante I, Landry P, Barat C, Janelle ME, Flamand L, Tremblay MJ, Provost P (2008) Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element. Nucleic Acids Res 36:2353–2365

    Article  PubMed  CAS  Google Scholar 

  • Pagans S, Kauder SE, Kaehlcke K, Sakane N, Schroeder S, Dormeyer W, Trievel RC, Verdin E, Schnolzer M, Ott M (2010) The Cellular lysine methyltransferase Set7/9-KMT7 binds HIV-1 TAR RNA monomethylates the viral transactivator Tat and enhances HIV transcription. Cell Host Microbe 7:234–244

    Article  PubMed  CAS  Google Scholar 

  • Palmer DK, O’Day K, Trong HL, Charbonneau H, Margolis RL (1991) Purification of the centromere-specific protein CENP-A and demonstration that it is a distinctive histone. Proc Natl Acad Sci U S A 88:3734–3738

    Article  PubMed  CAS  Google Scholar 

  • Parker R, Sheth U (2007) P bodies and the control of mRNA translation and degradation. Mol Cell 25:635–646

    Article  PubMed  CAS  Google Scholar 

  • Pearson R, Kim YK, Hokello J, Lassen K, Friedman J, Tyagi M, Karn J (2008) 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 82:12291–12303

    Article  PubMed  CAS  Google Scholar 

  • Pomerantz RJ, Trono D, Feinberg MB, Baltimore D (1990) Cells nonproductively infected with HIV-1 exhibit an aberrant pattern of viral RNA expression: a molecular model for latency. Cell 61:1271–1276

    Article  PubMed  CAS  Google Scholar 

  • Pomerantz RJ, Seshamma T, Trono D (1992) Efficient replication of human immunodeficiency virus type 1 requires a threshold level of Rev: potential implications for latency. J Virol 66:1809–1813

    PubMed  CAS  Google Scholar 

  • Rea S, Eisenhaber F, O’Carroll D, Strahl BD, Sun ZW, Schmid M, Opravil S, Mechtler K, Ponting CP, Allis CD, Jenuwein T (2000) Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406:593–599

    Article  PubMed  CAS  Google Scholar 

  • Reuse S, Calao M, Kabeya K, Guiguen A, Gatot JS, Quivy V, Vanhulle C, Lamine A, Vaira D, Demonte D, Martinelli V, Veithen E, Cherrier T, Avettand V, Poutrel S, Piette J, de Launoit Y, Moutschen M, Burny A, Rouzioux C, De Wit S, Herbein G, Rohr O, Collette Y, Lambotte O, Clumeck N, Van Lint C (2009) Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection. PLoS One 4:e6093

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg N, Jolicoeur P (1997) Retroviral pathogenesis. In: Coffin JM, Hughes SH, Varmus HE (eds) Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

    Google Scholar 

  • Ruddle NH, Armstrong MK, Richards FF (1976) Replication of murine leukemia virus in bone marrow-derived lymphocytes. Proc Natl Acad Sci U S A 73:3714–3718

    Article  PubMed  CAS  Google Scholar 

  • Saleh S, Solomon A, Wightman F, Xhilaga M, Cameron PU, Lewin SR (2007) CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T cells to HIV-1 infection: a novel model of HIV-1 latency. Blood 110:4161–4164

    Article  PubMed  CAS  Google Scholar 

  • Sahu GK, Cloyd MW (2011) Latent HIV in primary T lymphocytes is unresponsive to histone deacetylase inhibitors. Virol J 8:400

    Google Scholar 

  • Schroder AR, Shinn P, Chen H, Berry C, Ecker JR, Bushman F (2002) HIV-1 integration in the human genome favors active genes and local hotspots. Cell 110:521–529

    Article  PubMed  CAS  Google Scholar 

  • Schwartz O, Marechal V, Le Gall S, Lemonnier F, Heard JM (1996) Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med 2:338–342

    Article  PubMed  CAS  Google Scholar 

  • Scripture-Adams DD, Brooks DG, Korin YD, Zack JA (2002) Interleukin-7 induces expression of latent human immunodeficiency virus type 1 with minimal effects on T-cell phenotype. J Virol 76:13077–13082

    Article  PubMed  CAS  Google Scholar 

  • Sung TL, Rice AP (2006) Effects of prostratin on Cyclin T1/P-TEFb function and the gene expression profile in primary resting CD4+ T cells. Retrovirology 3:66

    Article  PubMed  CAS  Google Scholar 

  • Swingler S, Mann AM, Zhou J, Swingler C, Stevenson M (2007) Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein. PLoS Pathog 3:1281–1290

    Article  PubMed  CAS  Google Scholar 

  • Tong-Starksen SE, Luciw PA, Peterlin BM (1987) Human immunodeficiency virus long terminal repeat responds to T-cell activation signals. Proc Natl Acad Sci U S A 84:6845–6849

    Article  PubMed  CAS  Google Scholar 

  • Treand C, du Chéné I, Bres V, Kiernan R, Benarous R, Benkirane M, Emiliani S (2006) Requirement for SWI/SNF chromatin-remodeling complex in Tat-mediated activation of the HIV-1 promoter. EMBO J 25:1690–1699

    Article  PubMed  CAS  Google Scholar 

  • Triboulet R, Mari B, Lin YL, Chable-Bessia C, Bennasser Y, Lebrigand K, Cardinaud B, Maurin T, Barbry P, Baillat V, Reynes J, Corbeau P, Jeang KT, Benkirane M (2007) Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science 315:1579–1582

    Article  PubMed  CAS  Google Scholar 

  • Tyagi M, Karn J (2007) CBF-1 promotes transcriptional silencing during the establishment of HIV-1 latency. EMBO J 26:4985–4995

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Van Duyne R, Easley R, Wu W, Berro R, Pedati C, Klase Z, Kehn-Hall K, Flynn EK, Symer DE, Kashanchi F (2008) Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR. Retrovirology 5:40

    Article  PubMed  CAS  Google Scholar 

  • Varier RA, Kundu TK (2006) Chromatin modifications (acetylation/ deacetylation/ methylation) as new targets for HIV therapy. Curr Pharm Des 12:1975–1993

    Article  PubMed  CAS  Google Scholar 

  • Verdin E, Dequiedt F, Kasler HG (2003) Class II histone deacetylases: versatile regulators. Trends Genet 19:286–293

    Article  PubMed  CAS  Google Scholar 

  • Wang GP, Ciuffi A, Leipzig J, Berry CC, Bushman FD (2007) HIV integration site selection: analysis by massively parallel pyrosequencing reveals association with epigenetic modifications. Genome Res 17:1186–1194

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Ye L, Hou W, Zhou Y, Wang YJ, Metzger DS, Ho WZ (2009) Cellular microRNA expression correlates with susceptibility of monocytes/macrophages to HIV-1 infection. Blood 113:671–674

    Article  PubMed  CAS  Google Scholar 

  • Weissman JD, Brown JA, Howcroft TK, Hwang J, Chawla A, Roche PA, Schiltz L, Nakatani Y, Singer DS (1998) HIV-1 tat binds TAFII250 and represses TAFII250-dependent transcription of major histocompatibility class I genes. Proc Natl Acad Sci U S A 95:11601–11606

    Article  PubMed  CAS  Google Scholar 

  • Weissman JD, Hwang JR, Singer DS (2001) Extensive interactions between HIV TAT and TAF(II)250. Biochim Biophys Acta 1546:156–163

    Article  PubMed  CAS  Google Scholar 

  • Williams SA, Chen LF, Kwon H, Ruiz-Jarabo CM, Verdin E, Greene WC (2006) NF-kappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J 25:139–149

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Wong K, Sharma A, Awasthi S, Matlock EF, Rogers L, Van Lint C, Skiest DJ, Burns DK, Harrod R (2005) HIV-1 Tat interactions with p300 and PCAF transcriptional coactivators inhibit histone acetylation and neurotrophin signaling through CREB. J Biol Chem 280:9390–9399

    Article  PubMed  CAS  Google Scholar 

  • Xie B, Invernizzi CF, Richard S, Wainberg MA (2007) Arginine methylation of the human immunodeficiency virus type 1 Tat protein by PRMT6 negatively affects Tat Interactions with both cyclin T1 and the Tat transactivation region. J Virol 81:4226–4234

    Article  PubMed  CAS  Google Scholar 

  • Yang HC, Xing S, Shan L, O’Connell K, Dinoso J, Shen A, Zhou Y, Shrum CK, Han Y, Liu JO, Zhang H, Margolick JB, Siliciano RF (2009) Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation. J Clin Invest 119:3473–3486

    PubMed  CAS  Google Scholar 

  • Yeung ML, Bennasser Y, Myers TG, Jiang G, Benkirane M, Jeang KT (2005) Changes in microRNA expression profiles in HIV-1-transfected human cells. Retrovirology 2:81

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, Chen IS (1990) HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile latent viral structure. Cell 61:213–222

    Article  PubMed  CAS  Google Scholar 

  • Zhang H (2009) Reversal of HIV-1 latency with anti-microRNA inhibitors. Int J Biochem Cell Biol 41:451–454

    Article  PubMed  CAS  Google Scholar 

  • Zhou M, Halanski MA, Radonovich MF, Kashanchi F, Peng J, Price DH, Brady JN (2000) Tat modifies the activity of CDK9 to phosphorylate serine 5 of the RNA polymerase II carboxyl-terminal domain during human immunodeficiency virus type 1 transcription. Mol Cell Biol 20:5077–5086

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

Research work in DM laboratory was supported by NCCS and Department of Biotechnology (DBT), Government of India. ND is a CSIR senior research fellow (SRF) and PR is a research associate (RA) in DBT funded project.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Debashis Mitra .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Dhamija, N., Rawat, P., Mitra, D. (2013). Epigenetic Regulation of HIV-1 Persistence and Evolving Strategies for Virus Eradication. In: Kundu, T. (eds) Epigenetics: Development and Disease. Subcellular Biochemistry, vol 61. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4525-4_21

Download citation

Publish with us

Policies and ethics