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Past, present and future: 30 years of HIV research

Abstract

This year marks the thirtieth anniversary of the publication of the study that first reported the isolation of HIV-1. In this Timeline article, we provide a historical perspective of some of the major milestones in HIV science, highlighting how translational research has affected treatment and prevention of HIV. Finally, we discuss some of the current research directions and the scientific challenges ahead, in particular in the search for a cure for HIV.

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Figure 1
Figure 2: Schematic overview of the HIV-1 replication cycle.

References

  1. Gottlieb, M. S. et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N. Engl. J. Med. 305, 1425–1431 (1981).

    Article  CAS  PubMed  Google Scholar 

  2. Barre-Sinoussi, F. et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220, 868–871 (1983).

    Article  CAS  PubMed  Google Scholar 

  3. Popovic, M., Sarngadharan, M. G., Read, E. & Gallo, R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224, 497–500 (1984).

    Article  CAS  PubMed  Google Scholar 

  4. Levy, J. A. et al. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science 225, 840–842 (1984).

    Article  CAS  PubMed  Google Scholar 

  5. Schupbach, J. et al. Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. Science 224, 503–505 (1984).

    Article  CAS  PubMed  Google Scholar 

  6. Brun-Vezinet, F. et al. Detection of IgG antibodies to lymphadenopathy-associated virus in patients with AIDS or lymphadenopathy syndrome. Lancet 323, 1253–1256 (1984).

    Article  Google Scholar 

  7. Hahn, B. H. et al. Molecular cloning and characterization of the HTLV-III virus associated with AIDS. Nature 312, 166–169 (1984).

    Article  CAS  PubMed  Google Scholar 

  8. Luciw, P. A., Potter, S. J., Steimer, K., Dina, D. & Levy, J. A. Molecular cloning of AIDS-associated retrovirus. Nature 312, 760–763 (1984).

    Article  CAS  PubMed  Google Scholar 

  9. Alizon, M. et al. Molecular cloning of lymphadenopathy-associated virus. Nature 312, 757–760 (1984).

    Article  CAS  PubMed  Google Scholar 

  10. Wain-Hobson, S., Sonigo, P., Danos, O., Cole, S. & Alizon, M. Nucleotide sequence of the AIDS virus, LAV. Cell 40, 9–17 (1985).

    Article  CAS  PubMed  Google Scholar 

  11. Sanchez-Pescador, R. et al. Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science 227, 484–492 (1985).

    Article  CAS  PubMed  Google Scholar 

  12. Rabson, A. B. & Martin, M. A. Molecular organization of the AIDS retrovirus. Cell 40, 477–480 (1985).

    Article  CAS  PubMed  Google Scholar 

  13. Peeters, M. et al. Isolation and partial characterization of an HIV-related virus occurring naturally in chimpanzees in Gabon. AIDS 3, 625–630 (1989).

    Article  CAS  PubMed  Google Scholar 

  14. Hirsch, V. M., Olmsted, R. A., Murphey-Corb, M., Purcell, R. H. & Johnson, P. R. An African primate lentivirus (SIVsm) closely related to HIV-2. Nature 339, 389–392 (1989).

    Article  CAS  PubMed  Google Scholar 

  15. Dalgleish, A. G. et al. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312, 763–767 (1984).

    Article  CAS  PubMed  Google Scholar 

  16. Klatzmann, D. et al. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 312, 767–768 (1984).

    Article  CAS  PubMed  Google Scholar 

  17. Maddon, P. J. et al. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 47, 333–348 (1986).

    Article  CAS  PubMed  Google Scholar 

  18. Feng, Y., Broder, C. C., Kennedy, P. E. & Berger, E. A. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272, 872–877 (1996).

    Article  CAS  PubMed  Google Scholar 

  19. Weiss, R. A. Thirty years on: HIV receptor gymnastics and the prevention of infection. BMC Biol. 11, 57 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liu, R. et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86, 367–377 (1996).

    Article  CAS  PubMed  Google Scholar 

  21. Samson, M. et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382, 722–725 (1996).

    Article  CAS  PubMed  Google Scholar 

  22. Dean, M. et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273, 1856–1862 (1996).

    Article  CAS  PubMed  Google Scholar 

  23. Sheehy, A. M., Gaddis, N. C., Choi, J. D. & Malim, M. H. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418, 646–650 (2002).

    Article  CAS  PubMed  Google Scholar 

  24. Stremlau, M. et al. The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys. Nature 427, 848–853 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Neil, S. J., Zang, T. & Bieniasz, P. D. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451, 425–430 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. Van Damme, N. et al. The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 3, 245–252 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Laguette, N. et al. SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474, 654–657 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Piatak, M. Jr et al. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science 259, 1749–1754 (1993).

    Article  CAS  PubMed  Google Scholar 

  29. Pantaleo, G. et al. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature 362, 355–358 (1993).

    Article  CAS  PubMed  Google Scholar 

  30. Veazey, R. S. et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280, 427–431 (1998).

    Article  CAS  PubMed  Google Scholar 

  31. Brenchley, J. M. et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J. Exp. Med. 200, 749–759 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mehandru, S. et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J. Exp. Med. 200, 761–770 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Mattapallil, J. J. et al. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 434, 1093–1097 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Rey-Cuille, M. A. et al. Simian immunodeficiency virus replicates to high levels in sooty mangabeys without inducing disease. J. Virol. 72, 3872–3886 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Muller-Trutwin, M. C. et al. The evolutionary rate of nonpathogenic simian immunodeficiency virus (SIVagm) is in agreement with a rapid and continuous replication in vivo. Virology 223, 89–102 (1996).

    Article  CAS  PubMed  Google Scholar 

  36. Sodora, D. L. et al. Toward an AIDS vaccine: lessons from natural simian immunodeficiency virus infections of African nonhuman primate hosts. Nature Med. 15, 861–865 (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Lane, H. C. et al. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N. Engl. J. Med. 309, 453–458 (1983).

    Article  CAS  PubMed  Google Scholar 

  38. Brenchley, J. M. et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nature Med. 12, 1365–1371 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Alter, G. et al. HIV-1 adaptation to NK-cell-mediated immune pressure. Nature 476, 96–100 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Saah, A. J. et al. Association of HLA profiles with early plasma viral load, CD4+ cell count and rate of progression to AIDS following acute HIV-1 infection. AIDS 12, 2107–2113 (1998).

    Article  CAS  PubMed  Google Scholar 

  41. Migueles, S. A. et al. HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. Proc. Natl Acad. Sci. USA 97, 2709–2714 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Martin, M. P. et al. Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nature Genet. 31, 429–434 (2002).

    Article  CAS  PubMed  Google Scholar 

  43. Fischl, M. A. et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N. Engl. J. Med. 317, 185–191 (1987).

    Article  CAS  PubMed  Google Scholar 

  44. Mitsuya, H. et al. 3′-Azido-3′-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc. Natl Acad. Sci. USA 82, 7096–7100 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hammer, S. M. et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. N. Engl. J. Med. 337, 725–733 (1997).

    Article  CAS  PubMed  Google Scholar 

  46. Palella, F. J. Jr et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N. Engl. J. Med. 338, 853–860 (1998).

    Article  PubMed  Google Scholar 

  47. Ho, D. D. et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373, 123–126 (1995).

    Article  CAS  PubMed  Google Scholar 

  48. World Health Organization. Consolidated ARV guidelines (WHO, 2013).

  49. Bor, J., Herbst, A. J., Newell, M. L. & Barnighausen, T. Increases in adult life expectancy in rural South Africa: valuing the scale-up of HIV treatment. Science 339, 961–965 (2013).

    Article  CAS  PubMed  Google Scholar 

  50. Connor, E. M. et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N. Engl. J. Med. 331, 1173–1180 (1994).

    Article  CAS  PubMed  Google Scholar 

  51. Auvert, B. et al. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 trial. PLoS Med. 2, e298 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Bailey, R. C. et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 369, 643–656 (2007).

    Article  PubMed  Google Scholar 

  53. Gray, R. H. et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 369, 657–666 (2007).

    Article  PubMed  Google Scholar 

  54. Abdool Karim, Q. et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329, 1168–1174 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Grant, R. M. et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N. Engl. J. Med. 363, 2587–2599 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Van Damme, L. et al. Preexposure prophylaxis for HIV infection among African women. N. Engl. J. Med. 367, 411–422 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Jeanne Marrazzo, G. R., et al., in Conference on Retroviruses and Opportunistic Infections (International Antiviral Society-USA, 2013).

    Google Scholar 

  58. Cohen, M. S. et al. Prevention of HIV-1 infection with early antiretroviral therapy. N. Engl. J. Med. 365, 493–505 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Buchbinder, S. P., Katz, M. H., Hessol, N. A., O'Malley, P. M. & Holmberg, S. D. Long-term HIV-1 infection without immunologic progression. AIDS 8, 1123–1128 (1994).

    Article  CAS  PubMed  Google Scholar 

  60. Cao, Y., Qin, L., Zhang, L., Safrit, J. & Ho, D. D. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N. Engl. J. Med. 332, 201–208 (1995).

    Article  CAS  PubMed  Google Scholar 

  61. Rinaldo, C. et al. High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors. J. Virol. 69, 5838–5842 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Lambotte, O. et al. HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication. Clin. Infect. Dis. 41, 1053–1056 (2005).

    Article  PubMed  Google Scholar 

  63. Saez-Cirion, A. et al. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc. Natl Acad. Sci. USA 104, 6776–6781 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Betts, M. R. et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107, 4781–4789 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Saez-Cirion, A. et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI study. PLoS Pathog. 9, e1003211 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Persaud, D. et al. in Conference on Retroviruses and Opportunistic Infections. Abstract 48LB. (International Antiviral Society-USA, 2013).

    Google Scholar 

  67. Chun, T. W. et al. In vivo fate of HIV-1-infected T cells: quantitative analysis of the transition to stable latency. Nature Med. 1, 1284–1290 (1995).

    Article  CAS  PubMed  Google Scholar 

  68. Chun, T. W. et al. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc. Natl Acad. Sci. USA 94, 13193–13197 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Finzi, D. et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278, 1295–1300 (1997).

    Article  CAS  PubMed  Google Scholar 

  70. Wong, J. K. et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278, 1291–1295 (1997).

    Article  CAS  PubMed  Google Scholar 

  71. Lehrman, G. et al. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet 366, 549–555 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. J. Elliott, A. S. et al., in Conference on Retroviruses and Opportunistic Infections. Abstract 50LB. (International Antiviral Society-USA, 2013).

    Google Scholar 

  73. Hutter, G. et al. Long-term control of HIV by CCR5 Δ32/Δ32 stem-cell transplantation. N. Engl. J. Med. 360, 692–698 (2009).

    Article  PubMed  Google Scholar 

  74. Henrich, T. et al. in 7th International Conference on HIV pathogenesis, treatment and prevention. Abstract WELBA05. (International Antiviral Society-USA, 2013).

    Google Scholar 

  75. Cillo, A. R. et al. Plasma viremia and cellular HIV-1 DNA persist despite autologous hematopoietic stem cell transplantation for HIV-related lymphoma. J. Acquir. Immune Def. Syndr. 63, 438–441 (2013).

    Article  CAS  Google Scholar 

  76. Buchbinder, S. P. et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372, 1881–1893 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Gray, G. E. et al. Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study. Lancet Infect. Dis. 11, 507–515 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Rerks-Ngarm, S. et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med. 361, 2209–2220 (2009).

    Article  CAS  PubMed  Google Scholar 

  79. Kwong, P. D. et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393, 648–659 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Wei, X. et al. Antibody neutralization and escape by HIV-1. Nature 422, 307–312 (2003).

    Article  CAS  PubMed  Google Scholar 

  81. Zhou, T. et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 329, 811–817 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Wu, X. et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329, 856–861 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Walker, L. M. et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477, 466–470 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Klein, F. et al. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature 492, 118–122 (2012).

    Article  CAS  PubMed  Google Scholar 

  85. Watkins, J. D. et al. Anti-HIV IgA isotypes: differential virion capture and inhibition of transcytosis are linked to prevention of mucosal R5 SHIV transmission. AIDS 27, F13–F20 (2013).

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Françoise Barré-Sinoussi, Anna Laura Ross or Jean-François Delfraissy.

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Barré-Sinoussi, F., Ross, A. & Delfraissy, JF. Past, present and future: 30 years of HIV research. Nat Rev Microbiol 11, 877–883 (2013). https://doi.org/10.1038/nrmicro3132

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