HIV Latency and Reactivation: The Early Years

  • Guido Poli
Conference paper
Part of the Infectious Disease book series (ID)

Keywords

Virus Replication Virus Expression Upregulatory Effect Surrogate Model System Acute Viral Replication 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Notes

Acknowledgments

This chapter mostly relies on studies conducted during my stage in the Laboratory of Immuno-regulation at NIAID, NIH, Bethesda, MD. I wish to express my sincere gratitude to Tony Fauci and to all my friends and collaborators of that time for what I learned in those years. Whatever I have accomplished thereafter is the consequence of attending a very good school! This study is supported by my grant from the V° National Program of Research Against AIDS of the Istituto Superiore di Sanità, Rome, Italy.

References

  1. 1.
    Cullen BR, Greene WC (1989) Regulatory pathways governing HIV-1 replication. Cell 58:423–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzi-oux C, Rozenbaum W, Montagnier L (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868–871.PubMedCrossRefGoogle Scholar
  3. 3.
    Gallo RC, Sarin PS, Gelmann EP, Robert-Guroff M, Richardson E, Kalyanaraman VS, Mann D, Sidhu GD, Stahl RE, Zolla-Pazner S, Leibowitch J, Popovic M (1983) Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science 220:865–867.PubMedCrossRefGoogle Scholar
  4. 4.
    Klatzmann D, Champagne E, Chamaret S, Gruest J, Guetard D, Hercend T, Gluckman JC, Montagnier L (1984) T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 312:767–768.PubMedCrossRefGoogle Scholar
  5. 5.
    Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M (1986) The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233:215–219.PubMedCrossRefGoogle Scholar
  6. 6.
    Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, Janotta F, Aksamit A, Martin MA, Fauci AS (1986) Detection of AIDS virus in macrophages in brain tissue from AIDS patients with enceph-alopathy. Science 223:1089–1093.CrossRefGoogle Scholar
  7. 7.
    Feng Y, Broder CC, Kennedy PE, Berger EA (1996) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmem-brane, G protein-coupled receptor. Science 272:872–877.PubMedCrossRefGoogle Scholar
  8. 8.
    Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA (1996) CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macro-phage-tropic HIV-1. Science 272:1955–1958.PubMedCrossRefGoogle Scholar
  9. 9.
    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.PubMedCrossRefGoogle Scholar
  10. 10.
    Stevenson M (1997) Molecular mechanisms for the regulation of HIV replication, persistence and latency. AIDS 11S:25–33.Google Scholar
  11. 11.
    Mikovits JA, Young HA, Vertino P, Issa JP, Pitha PM, Turcoski-Corrales S, Taub DD, Petrow CL, Baylin SB, Ruscetti FW (1998) Infection with human immunodeficiency virus type 1 upregulates DNA methyltransferase, resulting in de novo meth-ylation of the gamma interferon (IFN-gamma) promoter and subsequent downregulation of IFN-gamma production. Mol Cell Biol 18:5166–5177.PubMedGoogle Scholar
  12. 12.
    Folks T, Powell DM, Lightfoote MM, Benn S, Martin MA, Fauci AS (1986) Induction of HTLV-III/LAV from a nonvi-rus-producing T-cell line: implications for latency. Science 231:600–602.PubMedCrossRefGoogle Scholar
  13. 13.
    Folks TM, Justement J, Kinter A, Schnittman S, Orenstein J, Poli G, Fauci AS (1988) Characterization of a promonocyte clone chronically infected with HIV and inducible by 13-phor-bol-12-myristate acetate. J Immunol 140:1117–1122.PubMedGoogle Scholar
  14. 14.
    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 USA 93:6377–6381.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedGoogle Scholar
  16. 16.
    Cannon P, Kim SH, Ulich C, Kim S (1994) Analysis of Tat function in human immunodeficiency virus type 1- infected low-level-expression cell lines U1 and ACH-2. J Virol 68: 1993 – 1997.PubMedGoogle Scholar
  17. 17.
    Clouse KA, Powell D, Washington I, Poli G, Strebel K, Farrar W, Barstad P, Kovacs J, Fauci AS, Folks TM (1989) Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. J Immunol 142:431– 438.PubMedGoogle Scholar
  18. 18.
    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 USA 86:5974–5978.PubMedCrossRefGoogle Scholar
  19. 19.
    Osborn L, Kunkel S, Nabel GJ (1989) Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci USA 86:2336–2340.PubMedCrossRefGoogle Scholar
  20. 20.
    Griffin GE, Leung K, Folks TM, Kunkel S, Nabel GJ (1991) Induction of NF-kappa B during monocyte differentiation is associated with activation of HIV-gene expression. Res Virol 142:233–238.PubMedCrossRefGoogle Scholar
  21. 21.
    Poli G, Kinter A, Justement JS, Kehrl JH, Bressler P, Stanley S, Fauci AS (1990) Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. Proc Natl Acad Sci USA 87:782–785.PubMedCrossRefGoogle Scholar
  22. 22.
    Poli G, Kinter AL, Fauci AS (1994) Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected U1 cells: inhibition of inductive effects by the interleukin 1 receptor antagonist. Proc Natl Acad Sci USA 91:108–112.PubMedCrossRefGoogle Scholar
  23. 23.
    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 mono-cytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms. J Exp Med 172:151–158.PubMedCrossRefGoogle Scholar
  24. 24.
    Yang X, Chen Y, Gabuzda D (1999) ERK MAP kinase links cytokine signals to activation of latent HIV-1 infection by stimulating a cooperative interaction of AP-1 and NF- kappaB. J Biol Chem 274:27,981–27,988.Google Scholar
  25. 25.
    Rizzi C, Crippa MP, Jeeninga RE, Berkhout B, Blasi F, Poli G, Alfano M (2006) Pertussis toxin B-oligomer suppresses IL-6 induced HIV-1 and chemokine expression in chronically infected U1 cells via inhibition of activator protein 1. J Immunol 176:999–1006.PubMedGoogle Scholar
  26. 26.
    Verdin E, Becker N, Bex F, Droogmans L, Burny A (1990) Identification and characterization of an enhancer in the coding region of the genome of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 87:4874–4878.PubMedCrossRefGoogle Scholar
  27. 27.
    Lint C, Ghysdael J, Paras P Jr Burny A, Verdin E (1994) A tran-scriptional regulatory element is associated with a nuclease-hypersensitive site in the pol gene of human immunodeficiency virus type 1. J Virol 68:2632–2648.PubMedGoogle Scholar
  28. 28.
    Poli G, Orenstein JM, Kinter A, Folks TM, Fauci AS (1989) Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines. Science 244:575–577.PubMedCrossRefGoogle Scholar
  29. 29.
    Walker CM, Moody DJ, Stites DP, Levy JA (1986) CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science 234:1563–1566.PubMedCrossRefGoogle Scholar
  30. 30.
    Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P (1995) Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV- suppressive factors produced by CD8+ T cells. Science 270:1811–1815.PubMedCrossRefGoogle Scholar
  31. 31.
    Baier M, Kurth R (1997) Fighting HIV-1 with IL-16. Nat Med 3:605–606.PubMedCrossRefGoogle Scholar
  32. 32.
    Maciaszek JW, Parada NA, Cruikshank WW, Center DM, Kornfeld H, Viglianti GA (1997) IL-16 represses HIV-1 promoter activity. J Immunol 158: 5–8.PubMedGoogle Scholar
  33. 33.
    Poli G, Kinter AL, Justement JS, Bressler P, Kehrl JH, Fauci AS (1991) Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage. J Exp Med 173: 589 – 597PubMedCrossRefGoogle Scholar
  34. 34.
    Poli G, Kinter AL, Justement JS, Bressler P, Kehrl JH, Fauci AS (1992) Retinoic acid mimics transforming growth factor beta in the regulation of human immunodeficiency virus expression in monocytic cells. Proc Natl Acad Sci USA 89:2689–2693.PubMedCrossRefGoogle Scholar
  35. 35.
    Lazdins JK, Klimkait T, Alteri E, Walker M, Woods-Cook K, Cox D, Bilbe G, Shipman R, Cerletti N, McMaster G (1991) TGF-beta: upregulator of HIV replication in macrophages. Res Virol 142:239–242.PubMedCrossRefGoogle Scholar
  36. 36.
  37. 37.
    Peterson PK, Gekker G, Chao CC, Schut R, Molitor TW, Balfour HH Jr(1991) Cocaine potentiates HIV-1 replication in human peripheral blood mononuclear cell cocultures. Involvement of transforming growth factor-beta. J Immunol 146:81–84.PubMedGoogle Scholar
  38. 38.
    Kootstra NA, van't Wout A, Huisman HG, Miedema F, Schuite-maker H (1994) Interference of interleukin-10 with human immunodeficiency virus type 1 replication in primary mono-cyte-derived macrophages. J Virol 68:6967–6975.PubMedGoogle Scholar
  39. 39.
    Weissman D, Poli G, Fauci AS (1994) Interleukin 10 blocks HIV replication in macrophages by inhibiting the autocrine loop of tumor necrosis factor alpha and interleukin 6 induction of virus. AIDS Res Hum Retroviruses 10:1199–1206.PubMedCrossRefGoogle Scholar
  40. 40.
    Weissman D, Poli G, Fauci AS (1995) IL-10 synergizes with multiple cytokines in enhancing HIV production in cells of monocytic lineage. J Acquir Immune Defic Syndr Hum Retro-virol 9:442–449.Google Scholar
  41. 41.
    Angel JB, SagetBM, Wang MZ, WangA,DinarelloCA,Skolnik PR (1995) Interleukin-10 enhances human immunodeficiency virus type 1 expression in a chronically infected promonocytic cell line (U1) by a tumor necrosis factor alpha-independent mechanism. J Interferon Cytokine Res 15:575–584.PubMedGoogle Scholar
  42. 42.
    Barcellini W, Rizzardi GP, Marriott JB, Fain C, Shattock RJ, Meroni PL, Poli G, Dalgleish AG (1996) Interleukin-10-induced HIV-1 expression is mediated by induction of both membrane-bound tumour necrosis factor (TNF)-alpha and TNF receptor type 1 in a promonocytic cell line. AIDS 10:835–842.PubMedCrossRefGoogle Scholar
  43. 43.
    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 176:739–750.PubMedCrossRefGoogle Scholar
  44. 44.
    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 68:2598–2604.PubMedGoogle Scholar
  45. 45.
    Alfano M, Poli G (2005) Role of cytokines and chemokines in the regulation of innate immunity and HIV infection. Mol Immunol 42:161–182.PubMedCrossRefGoogle Scholar
  46. 46.
    Kinter AL, Poli G, Fox L, Hardy E, Fauci AS (1995) HIV replication in IL-2-stimulated peripheral blood mononuclear cells is driven in an autocrine/paracrine manner by endogenous cyto-kines. J Immunol 154:2448–2459.PubMedGoogle Scholar
  47. 47.
    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 118:681–688.PubMedGoogle Scholar
  48. 48.
    Koot M, van Leeuwen R, de Goede RE, Keet IP, Danner S, Eeft-inck Schattenkerk JK, Reiss P, Tersmette M, Lange JM, Schuite-maker H (1999) Conversion rate towards a syncytium-inducing (SI) phenotype during different stages of human immunodeficiency virus type 1 infection and prognostic value of SI phenotype for survival after AIDS diagnosis. J Infect Dis 179:254–258.PubMedCrossRefGoogle Scholar
  49. 49.
    Vyakarnam A, McKeating J, Meager A, Beverley PC (1990) Tumour necrosis factors (α, β) induced by HIV-1 in peripheral blood mononuclear cells potentiate virus replication. AIDS 4:21–27.PubMedCrossRefGoogle Scholar
  50. 50.
    Kovacs JA, Baseler M, Dewar RJ, Vogel S, Davey RT Jr Falloon J, Polis MA, Walker RE, Stevens R, Salzman NP (1995) Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study. N Engl J Med 332:567–575.PubMedCrossRefGoogle Scholar
  51. 51.
    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.PubMedCrossRefGoogle Scholar
  52. 52.
    Emery S, Abrams DI, Cooper DA, Darbyshire JH, Lane HC, Lundgren JD, Neaton JD (2002) The evaluation of subcutaneous proleukin (interleukin-2) in a randomized international trial: rationale, design, and methods of ESPRIT. Control Clin Trials 23:198–220.PubMedCrossRefGoogle Scholar
  53. 53.
    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 USA 92:10,985–10,989.CrossRefGoogle Scholar
  54. 54.
    Barker E, Mackewicz CE, Levy JA (1995) Effects of TH1 and TH2 cytokines on CD8+ cell response against human immunodeficiency virus: implications for long-term survival. Proc Natl Acad Sci USA 92:11,135–11,139.CrossRefGoogle Scholar
  55. 55.
    Chun TW, Engel D, Mizell SB, Ehler LA, Fauci AS (1998) Induction of HIV-1 replication in latently infected CD4+ T cells using a combination of cytokines. J Exp Med 188:83–91.PubMedCrossRefGoogle Scholar
  56. 56.
    Uittenbogaart CH, Anisman DJ, Zack JA, Economides A, Schmid I, Hays EF (1994) Effects of cytokines on HIV-1 production by thymocytes. Thymus 23:155–175.PubMedGoogle Scholar
  57. 57.
    Smithgall MD, Wong JG, Critchett KE, Haffar OK (1996) IL-7 up-regulates HIV-1 replication in naturally infected peripheral blood mononuclear cells. J Immunol 156:2324–2330.PubMedGoogle Scholar
  58. 58.
    Ducrey-Rundquist O, Guyader M, Trono D (2002) Modalities of interleukin-7-induced human immunodeficiency virus permissiveness in quiescent T lymphocytes. J Virol 76:9103–9111.PubMedCrossRefGoogle Scholar
  59. 59.
    Wang FX, Xu Y, Sullivan J, Souder E, Argyris EG, Acheam-pong 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 115:128–137.PubMedGoogle Scholar
  60. 60.
    Bovolenta C, Camorali L, Lorini AL, Ghezzi S, Vicenzi E, Lazzarin A, Poli G (1999) Constitutive activation of STATs upon in vivo human immunodeficiency virus infection. Blood 94:4202–4209.PubMedGoogle Scholar
  61. 61.
    Crotti A, Lazzarin A, Bovolenta C, Poli G (2006) Negative regulation of HIV-1 expression by the natural isoform C-terminus truncated STAT5 (STAT5Delta). Retrovirology 3:S101.CrossRefGoogle Scholar
  62. 62.
    Pantaleo G, (1993) New concepts in the immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 328:327–335.PubMedCrossRefGoogle Scholar
  63. 63.
    Vicenzi E, Poli G (2005) Curr Prot Immunol 12.3.1–12.3.17.Google Scholar
  64. 64.
    Vicenzi E, et al (2007) Immunopathogenesis of HIV infection. In The Biology of Dendritic Cells: Role in the Pathogenesis and Immunity of HIV Infection (Gessani S, Belardelli F, ed.), Springer, New York.Google Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Guido Poli
    • 1
  1. 1.AIDS Immunopathogenesis UnitSan Raffaele Scientific InstituteMilanoItaly

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