Journal of Neuroimmune Pharmacology

, Volume 5, Issue 3, pp 278–293 | Cite as

Innate and Adaptive Factors Regulating Human Immunodeficiency Virus Type 1 Genomic Activation

  • Sonia Shah
  • Michael R. Nonnemacher
  • Vanessa Pirrone
  • Brian WigdahlEmail author


Over the past decade, antiretroviral therapy targeting the viral entry process, reverse transcriptase, integrase, and protease, has prolonged the lives of people infected with human immunodeficiency virus type 1 (HIV-1). However, despite the development of more effective therapeutic strategies, reservoirs of viral infection remain. This review discusses molecular mechanisms surrounding the development of latency from the site of integration to pre- and post-integration maintenance of latency, including epigenetic factors. In addition, an overview of innate and adaptive cells important to HIV-1 infection are examined from the viewpoint of cytokines released and cytokines that act on these cells to explore an overall understanding of HIV-1 proviral genome activation. Finally, this review is discussed from the viewpoint of how an understanding of the interplay of all of these factors will help guide the next generation of therapies.


HIV-1 transcription latency immune factors 



These studies were funded in part by the Public Health Service, National Institutes of Health through grants from the National Institute of Neurological Disorders and Stroke, NS32092 and NS46263, the National Institute of Drug Abuse, DA19807 (Dr. Brian Wigdahl, Principal Investigator), and under the Ruth L. Kirschstein National Research Service Award 5T32MH079785. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.


  1. Al-Harthi L, Roebuck KA, Landay A (1998) Induction of HIV-1 replication by type 1-like cytokines, interleukin (IL)-12 and IL-15: effect on viral transcriptional activation, cellular proliferation, and endogenous cytokine production. J Clin Immunol 18:124–131PubMedGoogle Scholar
  2. Albright AV, Vos RM, Gonzalez-Scarano F (2004) Low-level HIV replication in mixed glial cultures is associated with alterations in the processing of p55(Gag). Virology 325:328–339PubMedGoogle Scholar
  3. Alce TM, Popik W (2004) APOBEC3G is incorporated into virus-like particles by a direct interaction with HIV-1 Gag nucleocapsid protein. J Biol Chem 279:34083–34086PubMedGoogle Scholar
  4. Alexaki A, Wigdahl B (2008) HIV-1 infection of bone marrow hematopoietic progenitor cells and their role in trafficking and viral dissemination. PLoS Pathog 4:e1000215PubMedGoogle Scholar
  5. Alexaki A, Liu Y, Wigdahl B (2008) Cellular reservoirs of HIV-1 and their role in viral persistence. Curr HIV Res 6:388–400PubMedGoogle Scholar
  6. Alfano M, Crotti A, Vicenzi E, Poli G (2008) New players in cytokine control of HIV infection. Curr HIV/AIDS Rep 5:27–32PubMedGoogle Scholar
  7. Alter G, Altfeld M (2009) NK cells in HIV-1 infection: evidence for their role in the control of HIV-1 infection. J Intern Med 265:29–42PubMedGoogle Scholar
  8. An SF, Groves M, Gray F, Scaravilli F (1999) Early entry and widespread cellular involvement of HIV-1 DNA in brains of HIV-1 positive asymptomatic individuals. J Neuropathol Exp Neurol 58:1156–1162PubMedGoogle Scholar
  9. 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 23:1799–1806PubMedGoogle Scholar
  10. Barboric M, Nissen RM, Kanazawa S, Jabrane-Ferrat N, Peterlin BM (2001) NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. Mol Cell 8:327–337PubMedGoogle Scholar
  11. Barr SD, Leipzig J, Shinn P, Ecker JR, Bushman FD (2005) Integration targeting by avian sarcoma-leukosis virus and human immunodeficiency virus in the chicken genome. J Virol 79:12035–12044PubMedGoogle Scholar
  12. Berkhout B, Jeang KT (1992) Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat. J Virol 66:139–149PubMedGoogle Scholar
  13. Berkhout B, Gatignol A, Rabson AB, Jeang KT (1990) TAR-independent activation of the HIV-1 LTR: evidence that tat requires specific regions of the promoter. Cell 62:757–767PubMedGoogle Scholar
  14. Berry C, Hannenhalli S, Leipzig J, Bushman FD (2006) Selection of target sites for mobile DNA integration in the human genome. PLoS Comput Biol 2:e157PubMedGoogle Scholar
  15. Biswas P, Poli G, Kinter AL, Justement JS, Stanley SK, Maury WJ, Bressler P, Orenstein JM, Fauci AS (1992) Interferon gamma induces the expression of human immunodeficiency virus in persistently infected promonocytic cells (U1) and redirects the production of virions to intracytoplasmic vacuoles in phorbol myristate acetate-differentiated U1 cells. J Exp Med 176:739–750PubMedGoogle Scholar
  16. Biswas P, Poli G, Orenstein JM, Fauci AS (1994) Cytokine-mediated induction of human immunodeficiency virus (HIV) expression and cell death in chronically infected U1 cells: do tumor necrosis factor alpha and gamma interferon selectively kill HIV-infected cells? J Virol 68:2598–2604PubMedGoogle Scholar
  17. Boden D, Pusch O, Lee F, Tucker L, Ramratnam B (2003) Human immunodeficiency virus type 1 escape from RNA interference. J Virol 77:11531–11535PubMedGoogle Scholar
  18. Brack-Werner R, Kleinschmidt A, Ludvigsen A, Mellert W, Neumann M, Herrmann R, Khim MC, Burny A, Muller-Lantzsch N, Stavrou D et al (1992) Infection of human brain cells by HIV-1: restricted virus production in chronically infected human glial cell lines. AIDS 6:273–285PubMedGoogle Scholar
  19. Brady T, Agosto LM, Malani N, Berry CC, O’Doherty U, Bushman F (2009) HIV integration site distributions in resting and activated CD4+ T cells infected in culture. AIDS 23:1461–1471PubMedGoogle Scholar
  20. Bukrinsky MI, Stanwick TL, Dempsey MP, Stevenson M (1991) Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Science 254:423–427PubMedGoogle Scholar
  21. 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 89:6580–6584PubMedGoogle Scholar
  22. Burdo TH, Gartner S, Mauger D, Wigdahl B (2004a) Region-specific distribution of human immunodeficiency virus type 1 long terminal repeats containing specific configurations of CCAAT/enhancer-binding protein site II in brains derived from demented and nondemented patients. J Neurovirol 10(Suppl 1):7–14PubMedGoogle Scholar
  23. Burdo TH, Nonnemacher M, Irish BP, Choi CH, Krebs FC, Gartner S, Wigdahl B (2004b) High-affinity interaction between HIV-1 Vpr and specific sequences that span the C/EBP and adjacent NF-kappaB sites within the HIV-1 LTR correlate with HIV-1-associated dementia. DNA Cell Biol 23:261–269PubMedGoogle Scholar
  24. Burnett JC, Miller-Jensen K, Shah PS, Arkin AP, Schaffer DV (2009) Control of stochastic gene expression by host factors at the HIV promoter. PLoS Pathog 5:e1000260PubMedGoogle Scholar
  25. Bushman F, Lewinski M, Ciuffi A, Barr S, Leipzig J, Hannenhalli S, Hoffmann C (2005) Genome-wide analysis of retroviral DNA integration. Nat Rev Microbiol 3:848–858PubMedGoogle Scholar
  26. Byrnes AA, Harris DM, Atabani SF, Sabundayo BP, Langan SJ, Margolick JB, Karp CL (2008) Immune activation and IL-12 production during acute/early HIV infection in the absence and presence of highly active, antiretroviral therapy. J Leukoc Biol 84:1447–1453PubMedGoogle Scholar
  27. Cereseto A, Manganaro L, Gutierrez MI, Terreni M, Fittipaldi A, Lusic M, Marcello A, Giacca M (2005) Acetylation of HIV-1 integrase by p300 regulates viral integration. EMBO J 24:3070–3081PubMedGoogle Scholar
  28. Chen K, Huang J, Zhang C, Huang S, Nunnari G, Wang FX, Tong X, Gao L, Nikisher K, Zhang H (2006) Alpha interferon potently enhances the anti-human immunodeficiency virus type 1 activity of APOBEC3G in resting primary CD4 T cells. J Virol 80:7645–7657PubMedGoogle Scholar
  29. Cheng-Mayer C, Weiss C, Seto D, Levy JA (1989) Isolates of human immunodeficiency virus type 1 from the brain may constitute a special group of the AIDS virus. Proc Natl Acad Sci U S A 86:8575–8579PubMedGoogle Scholar
  30. 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 1:1284–1290PubMedGoogle Scholar
  31. Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, Chadwick K, Margolick J, Quinn TC, Kuo YH, Brookmeyer R, Zeiger MA, Barditch-Crovo P, Siliciano RF (1997) Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387:183–188PubMedGoogle Scholar
  32. 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 5:651–655PubMedGoogle Scholar
  33. Coburn GA, Cullen BR (2002) Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference. J Virol 76:9225–9231PubMedGoogle Scholar
  34. Coffin JM (1995) HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267:483–489PubMedGoogle Scholar
  35. Coleman CM, Wu L (2009) HIV interactions with monocytes and dendritic cells: viral latency and reservoirs. Retrovirology 6:51PubMedGoogle Scholar
  36. Cosenza MA, Zhao ML, Si Q, Lee SC (2002) Human brain parenchymal microglia express CD14 and CD45 and are productively infected by HIV-1 in HIV-1 encephalitis. Brain Pathol 12:442–455PubMedGoogle Scholar
  37. 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 74:6790–6799PubMedGoogle Scholar
  38. d'Adda di Fagagna F, Marzio G, Gutierrez MI, Kang LY, Falaschi A, Giacca M (1995) Molecular and functional interactions of transcription factor USF with the long terminal repeat of human immunodeficiency virus type 1. J Virol 69:2765–2775PubMedGoogle Scholar
  39. Davis LE, Hjelle BL, Miller VE, Palmer DL, Llewellyn AL, Merlin TL, Young SA, Mills RG, Wachsman W, Wiley CA (1992) Early viral brain invasion in iatrogenic human immunodeficiency virus infection. Neurology 42:1736–1739PubMedGoogle Scholar
  40. Demarchi F, D'Agaro P, Falaschi A, Giacca M (1993) In vivo footprinting analysis of constitutive and inducible protein–DNA interactions at the long terminal repeat of human immunodeficiency virus type 1. J Virol 67:7450–7460PubMedGoogle Scholar
  41. 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 289:312–326PubMedGoogle Scholar
  42. Diamond TL, Roshal M, Jamburuthugoda VK, Reynolds HM, Merriam AR, Lee KY, Balakrishnan M, Bambara RA, Planelles V, Dewhurst S, Kim B (2004) Macrophage tropism of HIV-1 depends on efficient cellular dNTP utilization by reverse transcriptase. J Biol Chem 279:51545–51553PubMedGoogle Scholar
  43. Dong C, Kwas C, Wu L (2009) Transcriptional restriction of human immunodeficiency virus type 1 gene expression in undifferentiated primary monocytes. J Virol 83:3518–3527PubMedGoogle Scholar
  44. Edelstein LC, Micheva-Viteva S, Phelan BD, Dougherty JP (2009) Short communication: activation of latent HIV type 1 gene expression by suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor approved for use to treat cutaneous T cell lymphoma. AIDS Res Hum Retroviruses 25:883–887PubMedGoogle Scholar
  45. Engelman A, Mizuuchi K, Craigie R (1991) HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer. Cell 67:1211–1221PubMedGoogle Scholar
  46. Fan L, Peden K (1992) Cell-free transmission of Vif mutants of HIV-1. Virology 190:19–29PubMedGoogle Scholar
  47. Farnet CM, Bushman FD (1997) HIV-1 cDNA integration: requirement of HMG I(Y) protein for function of preintegration complexes in vitro. Cell 88:483–492PubMedGoogle Scholar
  48. Festenstein R, Pagakis SN, Hiragami K, Lyon D, Verreault A, Sekkali B, Kioussis D (2003) Modulation of heterochromatin protein 1 dynamics in primary mammalian cells. Science 299:719–721PubMedGoogle Scholar
  49. Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, Margolick J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman DD, Siliciano RF (1997) Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278:1295–1300PubMedGoogle Scholar
  50. Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, Smith K, Lisziewicz J, Lori F, Flexner C, Quinn TC, Chaisson RE, Rosenberg E, Walker B, Gange S, Gallant J, Siliciano RF (1999) Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 5:512–517PubMedGoogle Scholar
  51. Fischer-Smith T, Croul S, Adeniyi A, Rybicka K, Morgello S, Khalili K, Rappaport J (2004) Macrophage/microglial accumulation and proliferating cell nuclear antigen expression in the central nervous system in human immunodeficiency virus encephalopathy. Am J Pathol 164:2089–2099PubMedGoogle Scholar
  52. Folks TM, Justement J, Kinter A, Schnittman S, Orenstein J, Poli G, Fauci AS (1988a) Characterization of a promonocyte clone chronically infected with HIV and inducible by 13-phorbol-12-myristate acetate. J Immunol 140:1117–1122PubMedGoogle Scholar
  53. Folks TM, Kessler SW, Orenstein JM, Justement JS, Jaffe ES, Fauci AS (1988b) Infection and replication of HIV-1 in purified progenitor cells of normal human bone marrow. Science 242:919–922PubMedGoogle Scholar
  54. Fraser C, Ferguson NM, Ghani AC, Prins JM, Lange JM, Goudsmit J, Anderson RM, de Wolf F (2000) Reduction of the HIV-1-infected T-cell reservoir by immune activation treatment is dose-dependent and restricted by the potency of antiretroviral drugs. AIDS 14:659–669PubMedGoogle Scholar
  55. Gao F, Robertson DL, Morrison SG, Hui H, Craig S, Decker J, Fultz PN, Girard M, Shaw GM, Hahn BH, Sharp PM (1996) The heterosexual human immunodeficiency virus type 1 epidemic in Thailand is caused by an intersubtype (A/E) recombinant of African origin. J Virol 70:7013–7029PubMedGoogle Scholar
  56. Gerritsen ME, Williams AJ, Neish AS, Moore S, Shi Y, Collins T (1997) CREB-binding protein/p300 are transcriptional coactivators of p65. Proc Natl Acad Sci U S A 94:2927–2932PubMedGoogle Scholar
  57. Gomez-Gonzalo M, Carretero M, Rullas J, Lara-Pezzi E, Aramburu J, Berkhout B, Alcami J, Lopez-Cabrera M (2001) The hepatitis B virus X protein induces HIV-1 replication and transcription in synergy with T-cell activation signals: functional roles of NF-kappaB/NF-AT and SP1-binding sites in the HIV-1 long terminal repeat promoter. J Biol Chem 276:35435–35443PubMedGoogle Scholar
  58. Granowitz EV, Saget BM, Wang MZ, Dinarello CA, Skolnik PR (1995) Interleukin 1 induces HIV-1 expression in chronically infected U1 cells: blockade by interleukin 1 receptor antagonist and tumor necrosis factor binding protein type 1. Mol Med 1:667–677PubMedGoogle Scholar
  59. Haase AT (1986) The AIDS lentivirus connection. Microb Pathog 1:1–4PubMedGoogle Scholar
  60. Han Y, Wind-Rotolo M, Yang HC, Siliciano JD, Siliciano RF (2007) Experimental approaches to the study of HIV-1 latency. Nat Rev Microbiol 5:95–106PubMedGoogle Scholar
  61. Harrich D, Garcia J, Mitsuyasu R, Gaynor R (1990) TAR independent activation of the human immunodeficiency virus in phorbol ester stimulated T lymphocytes. EMBO J 9:4417–4423PubMedGoogle Scholar
  62. Harris A, Bolus NE (2008) HIV/AIDS: an update. Radiol Technol 79:243–252, quiz 253–245PubMedGoogle Scholar
  63. He G, Margolis DM (2002) Counterregulation of chromatin deacetylation and histone deacetylase occupancy at the integrated promoter of human immunodeficiency virus type 1 (HIV-1) by the HIV-1 repressor YY1 and HIV-1 activator Tat. Mol Cell Biol 22:2965–2973PubMedGoogle Scholar
  64. Heider U, Rademacher J, Lamottke B, Mieth M, Moebs M, von Metzler I, Assaf C, Sezer O (2009) Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in cutaneous T cell lymphoma. Eur J Haematol 82:440–449PubMedGoogle Scholar
  65. Henderson AJ, Calame KL (1997) CCAAT/enhancer binding protein (C/EBP) sites are required for HIV-1 replication in primary macrophages but not CD4(+) T cells. Proc Natl Acad Sci U S A 94:8714–8719PubMedGoogle Scholar
  66. Henderson AJ, Zou X, Calame KL (1995) C/EBP proteins activate transcription from the human immunodeficiency virus type 1 long terminal repeat in macrophages/monocytes. J Virol 69:5337–5344PubMedGoogle Scholar
  67. Henderson AJ, Connor RI, Calame KL (1996) C/EBP activators are required for HIV-1 replication and proviral induction in monocytic cell lines. Immunity 5:91–101PubMedGoogle Scholar
  68. Henry KW, Wyce A, Lo WS, Duggan LJ, Emre NC, Kao CF, Pillus L, Shilatifard A, Osley MA, Berger SL (2003) Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8. Genes Dev 17:2648–2663PubMedGoogle Scholar
  69. Hickey WF, Vass K, Lassmann H (1992) Bone marrow-derived elements in the central nervous system: an immunohistochemical and ultrastructural survey of rat chimeras. J Neuropathol Exp Neurol 51:246–256PubMedGoogle Scholar
  70. Ho DD, Rota TR, Hirsch MS (1986) Infection of monocyte/macrophages by human T lymphotropic virus type III. J Clin Invest 77:1712–1715PubMedGoogle Scholar
  71. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M (1995) Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123–126PubMedGoogle Scholar
  72. Hoberg JE, Popko AE, Ramsey CS, Mayo MW (2006) IkappaB kinase alpha-mediated derepression of SMRT potentiates acetylation of RelA/p65 by p300. Mol Cell Biol 26:457–471PubMedGoogle Scholar
  73. Hogan TH, Nonnemacher MR, Krebs FC, Henderson A, Wigdahl B (2003a) HIV-1 Vpr binding to HIV-1 LTR C/EBP cis-acting elements and adjacent regions is sequence-specific. Biomed Pharmacother 57:41–48PubMedGoogle Scholar
  74. Hogan TH, Stauff DL, Krebs FC, Gartner S, Quiterio SJ, Wigdahl B (2003b) Structural and functional evolution of human immunodeficiency virus type 1 long terminal repeat CCAAT/enhancer binding protein sites and their use as molecular markers for central nervous system disease progression. J Neurovirol 9:55–68PubMedGoogle Scholar
  75. Holscher C, Holscher A, Ruckerl D, Yoshimoto T, Yoshida H, Mak T, Saris C, Ehlers S (2005) The IL-27 receptor chain WSX-1 differentially regulates antibacterial immunity and survival during experimental tuberculosis. J Immunol 174:3534–3544PubMedGoogle Scholar
  76. Ikeda K, Nagano K, Kawakami K (1993) Possible implications of Sp1-induced bending of DNA on synergistic activation of transcription. Gene 136:341–343PubMedGoogle Scholar
  77. Imai K, Okamoto T (2006) Transcriptional repression of human immunodeficiency virus type 1 by AP-4. J Biol Chem 281:12495–12505PubMedGoogle Scholar
  78. Imamichi T, Yang J, Huang DW, Brann TW, Fullmer BA, Adelsberger JW, Lempicki RA, Baseler MW, Lane HC (2008) IL-27, a novel anti-HIV cytokine, activates multiple interferon-inducible genes in macrophages. AIDS 22:39–45PubMedGoogle Scholar
  79. Jacque JM, Triques K, Stevenson M (2002) Modulation of HIV-1 replication by RNA interference. Nature 418:435–438PubMedGoogle Scholar
  80. 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 81:10914–10923PubMedGoogle Scholar
  81. Joel P, Shao W, Pratt K (1993) A nuclear protein with enhanced binding to methylated Sp1 sites in the AIDS virus promoter. Nucleic Acids Res 21:5786–5793PubMedGoogle Scholar
  82. Jones KA, Peterlin BM (1994) Control of RNA initiation and elongation at the HIV-1 promoter. Annu Rev Biochem 63:717–743PubMedGoogle Scholar
  83. Jordan A, Defechereux P, Verdin E (2001) The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation. EMBO J 20:1726–1738PubMedGoogle Scholar
  84. Jordan A, Bisgrove D, Verdin E (2003) HIV reproducibly establishes a latent infection after acute infection of T cells in vitro. EMBO J 22:1868–1877PubMedGoogle Scholar
  85. Kaehlcke K, Dorr A, Hetzer-Egger C, Kiermer V, Henklein P, Schnoelzer M, Loret E, Cole PA, Verdin E, Ott M (2003) Acetylation of Tat defines a cyclinT1-independent step in HIV transactivation. Mol Cell 12:167–176PubMedGoogle Scholar
  86. Kauder SE, Bosque A, Lindqvist A, Planelles V, Verdin E (2009) Epigenetic regulation of HIV-1 latency by cytosine methylation. PLoS Pathog 5:e1000495PubMedGoogle Scholar
  87. 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 18:6106–6118PubMedGoogle Scholar
  88. Kim YK, Bourgeois CF, Pearson R, Tyagi M, West MJ, Wong J, Wu SY, Chiang CM, Karn J (2006) Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency. EMBO J 25:3596–3604PubMedGoogle Scholar
  89. Kinter AL, Bende SM, Hardy EC, Jackson R, Fauci AS (1995) Interleukin 2 induces CD8+ T cell-mediated suppression of human immunodeficiency virus replication in CD4+ T cells and this effect overrides its ability to stimulate virus expression. Proc Natl Acad Sci U S A 92:10985–10989PubMedGoogle Scholar
  90. Klein SA, Klebba C, Kauschat D, Pape M, Ozmen L, Hoelzer D, Ottmann OG, Kalina U (2000) Interleukin-18 stimulates HIV-1 replication in a T-cell line. Eur Cytokine Netw 11:47–52PubMedGoogle Scholar
  91. Koelsch KK, Liu L, Haubrich R, May S, Havlir D, Gunthard HF, Ignacio CC, Campos-Soto P, Little SJ, Shafer R, Robbins GK, D’Aquila RT, Kawano Y, Young K, Dao P, Spina CA, Richman DD, Wong JK (2008) Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro. J Infect Dis 197:411–419PubMedGoogle Scholar
  92. Koot M, Keet IP, Vos AH, de Goede RE, Roos MT, Coutinho RA, Miedema F, Schellekens PT, Tersmette M (1993) Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med 118:681–688PubMedGoogle Scholar
  93. Korin YD, Zack JA (1999) Nonproductive human immunodeficiency virus type 1 infection in nucleoside-treated G0 lymphocytes. J Virol 73:6526–6532PubMedGoogle Scholar
  94. Kramer-Hammerle S, Rothenaigner I, Wolff H, Bell JE, Brack-Werner R (2005) Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus. Virus Res 111:194–213PubMedGoogle Scholar
  95. Lassen K, Han Y, Zhou Y, Siliciano J, Siliciano RF (2004) The multifactorial nature of HIV-1 latency. Trends Mol Med 10:525–531PubMedGoogle Scholar
  96. Lassmann H, Schmied M, Vass K, Hickey WF (1993) Bone marrow derived elements and resident microglia in brain inflammation. Glia 7:19–24PubMedGoogle Scholar
  97. 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 366:549–555PubMedGoogle Scholar
  98. Leonard J, Parrott C, Buckler-White AJ, Turner W, Ross EK, Martin MA, Rabson AB (1989) The NF-kappa B binding sites in the human immunodeficiency virus type 1 long terminal repeat are not required for virus infectivity. J Virol 63:4919–4924PubMedGoogle Scholar
  99. Lewinski MK, Bisgrove D, Shinn P, Chen H, Hoffmann C, Hannenhalli S, Verdin E, Berry CC, Ecker JR, Bushman FD (2005) Genome-wide analysis of chromosomal features repressing human immunodeficiency virus transcription. J Virol 79:6610–6619PubMedGoogle Scholar
  100. 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:e60PubMedGoogle Scholar
  101. Lim HG, Suzuki K, Cooper DA, Kelleher AD (2008) Promoter-targeted siRNAs induce gene silencing of simian immunodeficiency virus (SIV) infection in vitro. Mol Ther 16:565–570PubMedGoogle Scholar
  102. Liszewski MK, Yu JJ, O'Doherty U (2009) Detecting HIV-1 integration by repetitive-sampling Alu-gag PCR. Methods 47:254–260PubMedGoogle Scholar
  103. Maciaszek JW, Parada NA, Cruikshank WW, Center DM, Kornfeld H, Viglianti GA (1997) IL-16 represses HIV-1 promoter activity. J Immunol 158:5–8PubMedGoogle Scholar
  104. Madani N, Kabat D (2000) Cellular and viral specificities of human immunodeficiency virus type 1 vif protein. J Virol 74:5982–5987PubMedGoogle Scholar
  105. Managlia EZ, Landay A, Al-Harthi L (2006) Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway. Virology 350:443–452PubMedGoogle Scholar
  106. Marcello A (2006) Latency: the hidden HIV-1 challenge. Retrovirology 3:7PubMedGoogle Scholar
  107. Marshall HM, Ronen K, Berry C, Llano M, Sutherland H, Saenz D, Bickmore W, Poeschla E, Bushman FD (2007) Role of PSIP1/LEDGF/p75 in lentiviral infectivity and integration targeting. PLoS One 2:e1340PubMedGoogle Scholar
  108. Marzio G, Giacca M (1999) Chromatin control of HIV-1 gene expression. Genetica 106:125–130PubMedGoogle Scholar
  109. 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 95:13519–13524PubMedGoogle Scholar
  110. McAllister JJ, Phillips D, Millhouse S, Conner J, Hogan T, Ross HL, Wigdahl B (2000) Analysis of the HIV-1 LTR NF-kappaB-proximal Sp site III: evidence for cell type-specific gene regulation and viral replication. Virology 274:262–277PubMedGoogle Scholar
  111. McElrath MJ, Pruett JE, Cohn ZA (1989) Mononuclear phagocytes of blood and bone marrow: comparative roles as viral reservoirs in human immunodeficiency virus type 1 infections. Proc Natl Acad Sci U S A 86:675–679PubMedGoogle Scholar
  112. Merrill JE, Koyanagi Y, Chen IS (1989) Interleukin-1 and tumor necrosis factor alpha can be induced from mononuclear phagocytes by human immunodeficiency virus type 1 binding to the CD4 receptor. J Virol 63:4404–4408PubMedGoogle Scholar
  113. Miller MD, Farnet CM, Bushman FD (1997) Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition. J Virol 71:5382–5390PubMedGoogle Scholar
  114. Mitchell RS, Beitzel BF, Schroder AR, Shinn P, Chen H, Berry CC, Ecker JR, Bushman FD (2004) Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol 2:E234PubMedGoogle Scholar
  115. Nicholson JK, Cross GD, Callaway CS, McDougal JS (1986) In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). J Immunol 137:323–329PubMedGoogle Scholar
  116. Nielsen C, Pedersen C, Lundgren JD, Gerstoft J (1993) Biological properties of HIV isolates in primary HIV infection: consequences for the subsequent course of infection. AIDS 7:1035–1040PubMedGoogle Scholar
  117. Nonnemacher MR, Irish BP, Liu Y, Mauger D, Wigdahl B (2004) Specific sequence configurations of HIV-1 LTR G/C box array result in altered recruitment of Sp isoforms and correlate with disease progression. J Neuroimmunol 157:39–47PubMedGoogle Scholar
  118. O’Brien WA (1994) HIV-1 entry and reverse transcription in macrophages. J Leukoc Biol 56:273–277PubMedGoogle Scholar
  119. Oliva A, Kinter AL, Vaccarezza M, Rubbert A, Catanzaro A, Moir S, Monaco J, Ehler L, Mizell S, Jackson R, Li Y, Romano JW, Fauci AS (1998) Natural killer cells from human immunodeficiency virus (HIV)-infected individuals are an important source of CC-chemokines and suppress HIV-1 entry and replication in vitro. J Clin Invest 102:223–231PubMedGoogle Scholar
  120. Paci P, Carello R, Bernaschi M, D’Offizi G, Castiglione F (2009) Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy. BMC Infect Dis 9:172PubMedGoogle Scholar
  121. Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338:853–860PubMedGoogle Scholar
  122. Pazin MJ, Sheridan PL, Cannon K, Cao Z, Keck JG, Kadonaga JT, Jones KA (1996) NF-kappa B-mediated chromatin reconfiguration and transcriptional activation of the HIV-1 enhancer in vitro. Genes Dev 10:37–49PubMedGoogle Scholar
  123. Peluso R, Haase A, Stowring L, Edwards M, Ventura P (1985) A Trojan Horse mechanism for the spread of visna virus in monocytes. Virology 147:231–236PubMedGoogle Scholar
  124. Peng G, Lei KJ, Jin W, Greenwell-Wild T, Wahl SM (2006) Induction of APOBEC3 family proteins, a defensive maneuver underlying interferon-induced anti-HIV-1 activity. J Exp Med 203:41–46PubMedGoogle Scholar
  125. Peng G, Greenwell-Wild T, Nares S, Jin W, Lei KJ, Rangel ZG, Munson PJ, Wahl SM (2007) Myeloid differentiation and susceptibility to HIV-1 are linked to APOBEC3 expression. Blood 110:393–400PubMedGoogle Scholar
  126. Perkins ND, Felzien LK, Betts JC, Leung K, Beach DH, Nabel GJ (1997) Regulation of NF-kappaB by cyclin-dependent kinases associated with the p300 coactivator. Science 275:523–527PubMedGoogle Scholar
  127. Pierson TC, Zhou Y, Kieffer TL, Ruff CT, Buck C, Siliciano RF (2002) Molecular characterization of preintegration latency in human immunodeficiency virus type 1 infection. J Virol 76:8518–8531PubMedGoogle Scholar
  128. Pion M, Jordan A, Biancotto A, Dequiedt F, Gondois-Rey F, Rondeau S, Vigne R, Hejnar J, Verdin E, Hirsch I (2003) Transcriptional suppression of in vitro-integrated human immunodeficiency virus type 1 does not correlate with proviral DNA methylation. J Virol 77:4025–4032PubMedGoogle Scholar
  129. Poli G, Bressler P, Kinter A, Duh E, Timmer WC, Rabson A, Justement JS, Stanley S, Fauci AS (1990) Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms. J Exp Med 172:151–158PubMedGoogle Scholar
  130. Prins JM, Jurriaans S, van Praag RM, Blaak H, van Rij R, Schellekens PT, ten Berge IJ, Yong SL, Fox CH, Roos MT, de Wolf F, Goudsmit J, Schuitemaker H, Lange JM (1999) Immuno-activation with anti-CD3 and recombinant human IL-2 in HIV-1-infected patients on potent antiretroviral therapy. AIDS 13:2405–2410PubMedGoogle Scholar
  131. Quinones-Mateu ME, Mas A, Lain de Lera T, Soriano V, Alcami J, Lederman MM, Domingo E (1998) LTR and tat variability of HIV-1 isolates from patients with divergent rates of disease progression. Virus Res 57:11–20PubMedGoogle Scholar
  132. Rodriguez AR, Arulanandam BP, Hodara VL, McClure HM, Cobb EK, Salas MT, White R, Murthy KK (2007) Influence of interleukin-15 on CD8+ natural killer cells in human immunodeficiency virus type 1-infected chimpanzees. J Gen Virol 88:641–651PubMedGoogle Scholar
  133. Ross EK, Buckler-White AJ, Rabson AB, Englund G, Martin MA (1991) Contribution of NF-kappa B and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T-cell types. J Virol 65:4350–4358PubMedGoogle Scholar
  134. Ross HL, Gartner S, McArthur JC, Corboy JR, McAllister JJ, Millhouse S, Wigdahl B (2001a) HIV-1 LTR C/EBP binding site sequence configurations preferentially encountered in brain lead to enhanced C/EBP factor binding and increased LTR-specific activity. J Neurovirol 7:235–249PubMedGoogle Scholar
  135. Ross HL, Nonnemacher MR, Hogan TH, Quiterio SJ, Henderson A, McAllister JJ, Krebs FC, Wigdahl B (2001b) Interaction between CCAAT/enhancer binding protein and cyclic AMP response element binding protein 1 regulates human immunodeficiency virus type 1 transcription in cells of the monocyte/macrophage lineage. J Virol 75:1842–1856PubMedGoogle Scholar
  136. 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 110:521–529PubMedGoogle Scholar
  137. Shao W (1997) Characterization of HMBP-2, a DNA-binding protein that binds to HIV-1 LTR when only one of the three Sp1 sites is methylated. J Biomed Sci 4:39–46PubMedGoogle Scholar
  138. Shapiro L, Puren AJ, Barton HA, Novick D, Peskind RL, Shenkar R, Gu Y, Su MS, Dinarello CA (1998) Interleukin 18 stimulates HIV type 1 in monocytic cells. Proc Natl Acad Sci U S A 95:12550–12555PubMedGoogle Scholar
  139. Sheehy AM, Gaddis NC, Choi JD, Malim MH (2002) Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418:646–650PubMedGoogle Scholar
  140. Sheehy AM, Gaddis NC, Malim MH (2003) The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med 9:1404–1407PubMedGoogle Scholar
  141. Shirazi Y, Pitha PM (1992) Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle. J Virol 66:1321–1328PubMedGoogle Scholar
  142. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF (2003) Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med 9:727–728PubMedGoogle Scholar
  143. Siliciano JD, Lai J, Callender M, Pitt E, Zhang H, Margolick JB, Gallant JE, Cofrancesco J Jr, Moore RD, Gange SJ, Siliciano RF (2007) Stability of the latent reservoir for HIV-1 in patients receiving valproic acid. J Infect Dis 195:833–836PubMedGoogle Scholar
  144. Simon JH, Gaddis NC, Fouchier RA, Malim MH (1998) Evidence for a newly discovered cellular anti-HIV-1 phenotype. Nat Med 4:1397–1400PubMedGoogle Scholar
  145. Singh MK, Pauza CD (1992) Extrachromosomal human immunodeficiency virus type 1 sequences are methylated in latently infected U937 cells. Virology 188:451–458PubMedGoogle Scholar
  146. Smale ST (2003) The establishment and maintenance of lymphocyte identity through gene silencing. Nat Immunol 4:607–615PubMedGoogle Scholar
  147. Steger DJ, Workman JL (1997) Stable co-occupancy of transcription factors and histones at the HIV-1 enhancer. EMBO J 16:2463–2472PubMedGoogle Scholar
  148. Stellbrink HJ, van Lunzen J, Westby M, O'Sullivan E, Schneider C, Adam A, Weitner L, Kuhlmann B, Hoffmann C, Fenske S, Aries PS, Degen O, Eggers C, Petersen H, Haag F, Horst HA, Dalhoff K, Mocklinghoff C, Cammack N, Tenner-Racz K, Racz P (2002) Effects of interleukin-2 plus highly active antiretroviral therapy on HIV-1 replication and proviral DNA (COSMIC trial). AIDS 16:1479–1487PubMedGoogle Scholar
  149. Suyama M, Daikoku E, Goto T, Sano K, Morikawa Y (2009) Reactivation from latency displays HIV particle budding at plasma membrane, accompanying CD44 upregulation and recruitment. Retrovirology 6:63PubMedGoogle Scholar
  150. Suzuki K, Shijuuku T, Fukamachi T, Zaunders J, Guillemin G, Cooper D, Kelleher A (2005) Prolonged transcriptional silencing and CpG methylation induced by siRNAs targeted to the HIV-1 promoter region. J RNAi Gene Silencing 1:66–78PubMedGoogle Scholar
  151. Suzuki K, Juelich T, Lim H, Ishida T, Watanebe T, Cooper DA, Rao S, Kelleher AD (2008) Closed chromatin architecture is induced by an RNA duplex targeting the HIV-1 promoter region. J Biol Chem 283:23353–23363PubMedGoogle Scholar
  152. Takahashi K, Wesselingh SL, Griffin DE, McArthur JC, Johnson RT, Glass JD (1996) Localization of HIV-1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry. Ann Neurol 39:705–711PubMedGoogle Scholar
  153. Tesmer VM, Rajadhyaksha A, Babin J, Bina M (1993) NF-IL6-mediated transcriptional activation of the long terminal repeat of the human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 90:7298–7302PubMedGoogle Scholar
  154. Tornatore C, Chandra R, Berger JR, Major EO (1994) HIV-1 infection of subcortical astrocytes in the pediatric central nervous system. Neurology, 44(3 Pt 1):481–487PubMedGoogle Scholar
  155. Trillo-Pazos G, Diamanturos A, Rislove L, Menza T, Chao W, Belem P, Sadiq S, Morgello S, Sharer L, Volsky DJ (2003) Detection of HIV-1 DNA in microglia/macrophages, astrocytes and neurons isolated from brain tissue with HIV-1 encephalitis by laser capture microdissection. Brain Pathol 13:144–154PubMedGoogle Scholar
  156. Truong MJ, Darcissac EC, Hermann E, Dewulf J, Capron A, Bahr GM (1999) Interleukin-16 inhibits human immunodeficiency virus type 1 entry and replication in macrophages and in dendritic cells. J Virol 73:7008–7013PubMedGoogle Scholar
  157. Turner BM (1993) Decoding the nucleosome. Cell 75:5–8PubMedGoogle Scholar
  158. Tyagi M, Karn J (2007) CBF-1 promotes transcriptional silencing during the establishment of HIV-1 latency. EMBO J 26:4985–4995PubMedGoogle Scholar
  159. van Holde K, Zlatanova J (1996) What determines the folding of the chromatin fiber? Proc Natl Acad Sci U S A 93:10548–10555PubMedGoogle Scholar
  160. Van Lint C, Emiliani S, Ott M, Verdin E (1996) Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation. EMBO J 15:1112–1120PubMedGoogle Scholar
  161. Van Lint C, Amella CA, Emiliani S, John M, Jie T, Verdin E (1997) Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity. J Virol 71:6113–6127PubMedGoogle Scholar
  162. Van Maele B, Busschots K, Vandekerckhove L, Christ F, Debyser Z (2006) Cellular co-factors of HIV-1 integration. Trends Biochem Sci 31:98–105PubMedGoogle Scholar
  163. van Praag RM, Prins JM, Roos MT, Schellekens PT, Ten Berge IJ, Yong SL, Schuitemaker H, Eerenberg AJ, Jurriaans S, de Wolf F, Fox CH, Goudsmit J, Miedema F, Lange JM (2001) 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 21:218–226PubMedGoogle Scholar
  164. Verdin E (1991) 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 65:6790–6799PubMedGoogle Scholar
  165. Verdin E, Paras P Jr, Van Lint C (1993) Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation. EMBO J 12:3249–3259PubMedGoogle Scholar
  166. Volberding P, Demeter L, Bosch RJ, Aga E, Pettinelli C, Hirsch M, Vogler M, Martinez A, Little S, Connick E (2009) Antiretroviral therapy in acute and recent HIV infection: a prospective multicenter stratified trial of intentionally interrupted treatment. AIDS 23:1987–1995PubMedGoogle Scholar
  167. von Briesen H, von Mallinckrodt C, Esser R, Muller S, Becker K, Rubsamen-Waigmann H, Andreesen R (1991) Effect of cytokines and lipopolysaccharides on HIV infection of human macrophages. Res Virol 142:197–204Google Scholar
  168. Wang Z, Trillo-Pazos G, Kim SY, Canki M, Morgello S, Sharer LR, Gelbard HA, Su ZZ, Kang DC, Brooks AI, Fisher PB, Volsky DJ (2004) Effects of human immunodeficiency virus type 1 on astrocyte gene expression and function: potential role in neuropathogenesis. J Neurovirol 10(Suppl 1):25–32PubMedGoogle Scholar
  169. Wang FX, Xu Y, Sullivan J, Souder E, Argyris EG, Acheampong EA, Fisher J, Sierra M, Thomson MM, Najera R, Frank I, Kulkosky J, Pomerantz RJ, Nunnari G (2005) IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART. J Clin Invest 115:128–137PubMedGoogle Scholar
  170. 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 17:1186–1194PubMedGoogle Scholar
  171. Watkins BA, Dorn HH, Kelly WB, Armstrong RC, Potts BJ, Michaels F, Kufta CV, Dubois-Dalcq M (1990) Specific tropism of HIV-1 for microglial cells in primary human brain cultures. Science 249:549–553PubMedGoogle Scholar
  172. Weinberger LS, Burnett JC, Toettcher JE, Arkin AP, Schaffer DV (2005) Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Cell 122:169–182PubMedGoogle Scholar
  173. WHO/UNAIDS (2007) Joint United Nations Programme on HIV/AIDS/World Helath Organization AIDS epidemic update.Google Scholar
  174. Wiech NL, Fisher JF, Helquist P, Wiest O (2009) Inhibition of histone deacetylases: a pharmacological approach to the treatment of non-cancer disorders. Curr Top Med Chem 9:257–271PubMedGoogle Scholar
  175. Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MB (1986) Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A 83:7089–7093PubMedGoogle Scholar
  176. Williams KC, Corey S, Westmoreland SV, Pauley D, Knight H, deBakker C, Alvarez X, Lackner AA (2001) Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS. J Exp Med 193:905–915PubMedGoogle Scholar
  177. 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 25:139–149PubMedGoogle Scholar
  178. 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 81:6043–6056PubMedGoogle Scholar
  179. Wolffe AP (1994) Transcription: in tune with the histones. Cell 77:13–16PubMedGoogle Scholar
  180. Wolffe AP, Pruss D (1996) Targeting chromatin disruption: transcription regulators that acetylate histones. Cell 84:817–819PubMedGoogle Scholar
  181. Wong JK, Hezareh M, Gunthard HF, Havlir DV, Ignacio CC, Spina CA, Richman DD (1997) Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278:1291–1295PubMedGoogle Scholar
  182. Wu X, Li Y, Crise B, Burgess SM (2003) Transcription start regions in the human genome are favored targets for MLV integration. Science 300:1749–1751PubMedGoogle Scholar
  183. Yamagishi M, Ishida T, Miyake A, Cooper DA, Kelleher AD, Suzuki K, Watanabe T (2009) Retroviral delivery of promoter-targeted shRNA induces long-term silencing of HIV-1 transcription. Microbes Infect 11:500–508PubMedGoogle Scholar
  184. Yoder KE, Bushman FD (2000) Repair of gaps in retroviral DNA integration intermediates. J Virol 74:11191–11200PubMedGoogle Scholar
  185. 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 61:213–222PubMedGoogle Scholar
  186. Zhang S, Pointer D, Singer G, Feng Y, Park K, Zhao LJ (1998) Direct binding to nucleic acids by Vpr of human immunodeficiency virus type 1. Gene 212:157–166PubMedGoogle Scholar
  187. Zhou Y, Zhang H, Siliciano JD, Siliciano RF (2005) Kinetics of human immunodeficiency virus type 1 decay following entry into resting CD4+ T cells. J Virol 79:2199–2210PubMedGoogle Scholar
  188. Zhu T, Wang N, Carr A, Nam DS, Moor-Jankowski R, Cooper DA, Ho DD (1996) Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission. J Virol 70:3098–3107PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Sonia Shah
    • 1
    • 2
    • 3
    • 4
  • Michael R. Nonnemacher
    • 1
    • 2
    • 3
    • 4
  • Vanessa Pirrone
    • 1
    • 2
    • 3
    • 4
  • Brian Wigdahl
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of Microbiology and ImmunologyDrexel University College of MedicinePhiladelphiaUSA
  2. 2.Center for Molecular Virology and Translational NeuroscienceDrexel University College of Medicine School of MedicinePhiladelphiaUSA
  3. 3.Center for Molecular Therapeutics and ResistanceDrexel University College of Medicine School of MedicinePhiladelphiaUSA
  4. 4.Institute for Molecular Medicine and Infectious DiseaseDrexel University College of Medicine School of MedicinePhiladelphiaUSA

Personalised recommendations