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HIV-1 pathogenesis

Nature Medicine volume 9, pages 853–860 (2003)Cite this article

Abstract

Despite considerable advances in HIV science in the past 20 years, the reason why HIV-1 infection is pathogenic is still debated and the goal of eradicating HIV-1 infection remains elusive. A deeper understanding of the interplay between HIV-1 and its host and why simian immunodeficiency virus (SIV) is nonpathogenic in some natural hosts may provide a few answers.

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Figure 1: Summary of some research highlights in viral pathogenesis, with emphasis on the areas of viral reservoirs, viral pathogenicity and host cell factors.

Katie Ris

Figure 2: An overview of viral reservoirs and their relative contribution to plasma viremia.

Katie Ris

Figure 3: Viral replication patterns in different host cells.

Katie Ris

Figure 4: Summary of the cellular factors that promote or inhibit HIV-1 replication.

Katie Ris

Figure 5: Summary of the mechanisms that mediate direct and indirect viral cytopathogenicity.

Katie Ris

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References

  1. 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).

    CAS  PubMed  Google Scholar 

  2. Popovic, M., 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).

    CAS  PubMed  Google Scholar 

  3. Levy, J.A., Hoffman, A.D., Kramer, S.M., Landis, J.A. & Shimabukuro, J.M. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science 225, 840–842 (1984).

    CAS  PubMed  Google Scholar 

  4. 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).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  6. 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).

    CAS  PubMed  Google Scholar 

  7. Choe, H. et al. The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 85, 1135–1148 (1996).

    CAS  PubMed  Google Scholar 

  8. Deng, H. et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 381, 661–666 (1996).

    CAS  PubMed  Google Scholar 

  9. Alkhatib, G. et al. CC CKR5: a RANTES, MIP-1α, MIP-1β receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272, 1955–1958 (1996).

    CAS  PubMed  Google Scholar 

  10. Dragic, T. et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 381, 667–673 (1996).

    CAS  PubMed  Google Scholar 

  11. Perelson, A.S. Modelling viral and immune system dynamics. Nat. Rev. Immunol. 2, 28–36 (2002).

    CAS  PubMed  Google Scholar 

  12. Wei, X. et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373, 117–122 (1995).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  14. Schnittman, S.M. et al. The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science 245, 305–308 (1989).

    CAS  PubMed  Google Scholar 

  15. Adams, M. et al. Cellular latency in human immunodeficiency virus-infected individuals with high CD4 levels can be detected by the presence of promoter-proximal transcripts. Proc. Natl. Acad. Sci. USA 91, 3862–3866 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Seshamma, T., Bagasra, O., Trono, D., Baltimore, D. & Pomerantz, R. Blocked early-stage latency in the peripheral blood cells of certain individuals infected with human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. USA 89, 10663–10667 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Chun, T.W. et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387, 183–188 (1997).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  19. Wong, J.K. et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278, 1291–1227 (1997).

    CAS  PubMed  Google Scholar 

  20. Zack, J.A. et al. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell 61, 213–222 (1990).

    CAS  PubMed  Google Scholar 

  21. Stevenson, M., Stanwick, T.L., Dempsey, M.P. & Lamonica, C.A. HIV-1 replication is controlled at the level of T cell activation and proviral integration. EMBO J. 9, 1551–1560 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang, Z. et al. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science 286, 1353–1357 (1999).

    CAS  PubMed  Google Scholar 

  23. Unutmaz, D., Kewal-Ramani, V.N., Marmon, S. & Littman, D.R. Cytokine signals are sufficient for HIV-1 infection of resting human T lymphocytes. J. Exp. Med. 189, 1735–1746 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Eckstein, D.A. et al. HIV-1 actively replicates in naive CD4+ T cells residing within human lymphoid tissues. Immunity 15, 671–82 (2001).

    CAS  PubMed  Google Scholar 

  25. Spina, C.A., Kwoh, T.J., Chowers, M.Y., Guatelli, J.C. & Richman, D.D. The importance of nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes. J. Exp. Med. 179, 115–123 (1994).

    CAS  PubMed  Google Scholar 

  26. Miller, M.D., Warmerdam, M.T., Gaston, I., Greene, W.C. & Feinberg, M.B. The human immunodeficiency virus-1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages. J. Exp. Med. 179, 101–13 (1994).

    CAS  PubMed  Google Scholar 

  27. Swingler, S. et al. HIV-1 Nef intersects the CD40L signaling pathway in macrophages to promote resting cell infection. Nature (in the press).

  28. Wu, Y. & Marsh, J.W. Selective transcription and modulation of resting T cell activity by preintegrated HIV DNA. Science 293, 1503–1506 (2001).

    CAS  PubMed  Google Scholar 

  29. Schroder, A.R. et al. HIV-1 integration in the human genome favors active genes and local hotspots. Cell 110, 521–529 (2002).

    CAS  PubMed  Google Scholar 

  30. Jordan, A., Defechereux, P. & Verdin, E. The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation. EMBO J. 20, 1726–38 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Gartner, S. et al. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233, 215–219 (1986).

    CAS  PubMed  Google Scholar 

  32. Koenig, S. et al. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233, 1089–1093 (1986).

    CAS  PubMed  Google Scholar 

  33. Wiley, C.A., Schrier, R.D., Nelson, J.A., Lampert, P.W. & Oldstone, M.B.A. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc. Natl. Acad. Sci. USA 83, 7089–7093 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Weinberg, J.B., Matthews, T.J., Cullen, B.R. & Malim, M.H. Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes. J. Exp. Med. 174, 1477–1482 (1991).

    CAS  PubMed  Google Scholar 

  35. Bukrinsky, M.I. et al. Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc. Natl. Acad. Sci. USA 89, 6580–6584 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Lewis, P., Hensel, M. & Emerman, M. Human immunodeficiency virus infection of cells arrested in the cell cycle. EMBO J. 11, 3053–3058 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 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).

    CAS  PubMed  Google Scholar 

  38. 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).

    CAS  PubMed  Google Scholar 

  39. 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).

    CAS  PubMed  Google Scholar 

  40. 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).

    CAS  PubMed  Google Scholar 

  41. Igarashi, T. et al. Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans. Proc. Natl. Acad. Sci. USA 98, 658–663 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Eckstein, D.A. et al. HIV-1 Vpr enhances viral burden by facilitating infection of tissue macrophages but not nondividing CD4+ T cells. J. Exp. Med. 194, 1407–1419 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Embretson, J. et al. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature 362, 359–362 (1993).

    CAS  PubMed  Google Scholar 

  44. Orenstein, J.M., Meltzer, M.S., Phipps, T. & Gendelman, H.E. Cytoplasmic Assembly and accumulation of human immunodeficiency virus types 1 and 2 in recombinant human colony-stimulating factor-1-treated human monocytes: An ultrastructural study. J. Virol. 62, 2578–2586 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Raposo, G. et al. Human macrophages accumulate HIV-1 particles in MHC II compartments. Traffic 3, 718–729 (2002).

    CAS  PubMed  Google Scholar 

  46. Muller, H., Falk, S. & Stutte, H.J. Accessory cells as primary target of human immunodeficiency virus HIV infection. J. Clin. Pathol. 39, 1161 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Le Tourneau, A. et al. Viral type particles in the germinal centers during a lymphadenopathic syndrome related to AIDS. Ann. Pathol. 5, 137–142 (1985).

    CAS  PubMed  Google Scholar 

  48. Tenner-Racz, K. et al. HTLV-III/LAV viral antigens in lymph nodes of homosexual men with persistent generalized lymphadenopathy and AIDS. Am. J. Pathol. 123, 9–15 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Tschachler, E. et al. Epidermal Langerhans cells—a target for HTLV-III/LAV infection. J. Invest. Dermatol. 88, 233–237 (1987).

    CAS  PubMed  Google Scholar 

  50. Patterson, S. & Knight, S.C. Susceptibility of human peripheral blood dendritic cells to infection by human immunodeficiency virus. J. Gen. Virol. 68, 1177–1181 (1987).

    PubMed  Google Scholar 

  51. Spiegel, H., Herbst, H., Niedobitek, G., Foss, H.D. & Stein, H. Follicular dendritic cells are a major reservoir for human immunodeficiency virus type 1 in lymphoid tissues facilitating infection of CD4+ T-helper cells. Am. J. Pathol. 140, 15–22 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 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).

    CAS  PubMed  Google Scholar 

  53. Cameron, P.U. et al. Dendritic cells exposed to human immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells. Science 257, 383–387 (1992).

    CAS  PubMed  Google Scholar 

  54. Pope, M. et al. Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell 78, 389–398 (1994).

    CAS  PubMed  Google Scholar 

  55. Geijtenbeek, T.B. et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 100, 587–597 (2000).

    CAS  PubMed  Google Scholar 

  56. Turville, S.G. et al. Diversity of receptors binding HIV on dendritic cell subsets. Nat. Immunol. 3, 975–983 (2002).

    CAS  PubMed  Google Scholar 

  57. Kwon, D.S., Gregorio, G., Bitton, N., Hendrickson, W.A. & Littman, D.R. DC-SIGN-mediated internalization of HIV is required for trans-enhancement of T cell infection. Immunity 16, 135–144 (2002).

    CAS  PubMed  Google Scholar 

  58. Smith, B.A. et al. Persistence of infectious HIV on follicular dendritic cells. J. Immunol. 166, 690–696 (2001).

    CAS  PubMed  Google Scholar 

  59. Moore, J. & Stevenson, M. New targets for inhibitors of HIV-1 replication. Nat. Rev. Mol. Cell Biol. 1, 40–49 (2000).

    CAS  PubMed  Google Scholar 

  60. Ratner, L. et al. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 313, 277–284 (1985).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  63. Wong-Staal, F. et al. Genomic diversity of human T-lymphotropic virus type III (HTLV-III). Science 229, 759–762 (1985).

    CAS  PubMed  Google Scholar 

  64. Arya, S.K., Guo, C., Josephs, S.F. & Wong-Staal, F. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science 229, 69–73 (1985).

    CAS  PubMed  Google Scholar 

  65. Sodroski, J., Patarca, R. & Rosen, C. Location of the trans-activating region of the genome of human T cell lymphotropic virus type III. Science 229, 74–77 (1985).

    CAS  PubMed  Google Scholar 

  66. Wright, C.M., Felder, B.K., Paskalis, H. & Pavlakis, G.N. Expression and characterization of the trans-activator of HTLV-III/LAV virus. Science 234, 988–992 (1986).

    CAS  PubMed  Google Scholar 

  67. Sodroski, J. et al. A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature 321, 412–417 (1986).

    CAS  PubMed  Google Scholar 

  68. Cullen, B.R. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell 46, 973–982 (1986).

    CAS  PubMed  Google Scholar 

  69. Cohen, E.A., Terwilliger, E.F., Sodroski, J.G. & Haseltine, W.A. Identification of a protein encoded by the vpu gene of HIV-1. Nature 334, 532–534 (1988).

    CAS  PubMed  Google Scholar 

  70. Strebel, K., Klimkait, T. & Martin, M.A. A novel gene of HIV-1, vpu, and its 16-kilodalton product. Science 241, 1221–1223 (1988).

    CAS  PubMed  Google Scholar 

  71. Arya, S.K. & Gallo, R.C. Three novel genes of human T-lymphotropic virus type III: immune reactivity of their products with sera from acquired immune deficiency syndrome patients. Proc. Natl. Acad. Sci. USA 83, 2209–2213 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Strebel, K. et al. The HIV 'A' (sor) gene product is essential for virus infectivity. Nature 328, 728–730 (1987).

    CAS  PubMed  Google Scholar 

  73. Fisher, A.G. et al. The sor gene of HIV-1 is required for efficient virus transmission in vitro. Science 237, 888–893 (1987).

    CAS  PubMed  Google Scholar 

  74. Kestler, H.W. et al. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell 65, 651–662 (1991).

    CAS  PubMed  Google Scholar 

  75. Cocchi, F. et al. Identification of RANTES, MIP-1α, and MIP-1β as the major HIV-suppressive factors produced by CD8+ T Cells. Science 270, 1811–1815 (1995).

    CAS  PubMed  Google Scholar 

  76. Kinoshita, S., Chen, B.K., Kaneshima, H. & Nolan, G.P. Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells. Cell 95, 595–604 (1998).

    CAS  PubMed  Google Scholar 

  77. Kalpana, G.V., Marmon, S., Wang, W., Crabtree, G.R. & Goff, S.P. Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5. Science 266, 2002–2006 (1994).

    CAS  PubMed  Google Scholar 

  78. Farnet, C.M. & Bushman, F.D. HIV-1 cDNA integration: requirement of HMG I(Y) protein for function of preintegration complexes in vitro. Cell 88, 483–492 (1997).

    CAS  PubMed  Google Scholar 

  79. Chen, H. & Engelman, A. The barrier-to-autointegration protein is a host factor for HIV type 1 integration. Proc. Natl. Acad. Sci. USA 95, 15270–15274 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Wei, P., Garber, M.E., Fang, S.M., Fischer, W.H. & Jones, K.A. A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA. Cell 92, 451–462 (1998).

    CAS  PubMed  Google Scholar 

  81. Fornerod, M., Ohno, M., Yoshida, M. & Mattaj, I.W. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 90, 1051–1060 (1997).

    CAS  PubMed  Google Scholar 

  82. Fukuda, M. et al. CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature 390, 308–311 (1997).

    CAS  PubMed  Google Scholar 

  83. Neville, M., Stutz, F., Lee, L., Davis, L.I. & Rosbash, M. The importin-β family member Crm1p bridges the interaction between Rev and the nuclear pore complex during nuclear export. Curr. Biol. 7, 767–775 (1997).

    CAS  PubMed  Google Scholar 

  84. Franke, E.K., Yuan, H.E.H. & Luban, J. Specific incorporation of cyclophilin A into HIV-1 virions. Nature 372, 359–362 (1994).

    CAS  PubMed  Google Scholar 

  85. Thali, M. et al. Functional association of cyclophilin A with HIV-1 virions. Nature 372, 363–365 (1994).

    CAS  PubMed  Google Scholar 

  86. Zimmerman, C. et al. Identification of a host protein essential for assembly of immature HIV-1 capsids. Nature 415, 88–92 (2002).

    CAS  PubMed  Google Scholar 

  87. Garrus, J.E. et al. Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 107, 55–65 (2001).

    CAS  PubMed  Google Scholar 

  88. VerPlank, L. et al. Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55(Gag). Proc. Natl. Acad. Sci. USA 98, 7724–7729 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Madani, N. & Kabat, D. An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein. J. Virol. 72, 10251–10255 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Simon, J.H.M., Gaddis, N.C., Fouchier, R.A.M. & Malim, M.H. Evidence for a newly discovered cellular anti-HIV-1 phenotype. Nat. Med. 4, 1397–1400 (1998).

    CAS  PubMed  Google Scholar 

  91. 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).

    CAS  PubMed  Google Scholar 

  92. Munk, C., Brandt, S.M., Lucero, G. & Landau, N.R. A dominant block to HIV-1 replication at reverse transcription in simian cells. Proc. Natl. Acad. Sci. USA 99, 13843–13848 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Hatziioannou, T., Cowan, S., Goff, S.P., Bieniasz, P.D. & Towers, G.J. Restriction of multiple divergent retroviruses by Lv1 and Ref1. EMBO J. 22, 385–394 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Cullen, B.R. RNA interference: antiviral defense and genetic tool. Nat. Immunol. 3, 597–599 (2002).

    CAS  PubMed  Google Scholar 

  95. 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).

    CAS  PubMed  Google Scholar 

  96. Mellors, J.W. et al. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272, 1167–1170 (1996).

    CAS  PubMed  Google Scholar 

  97. Deacon, N.J. et al. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 270, 988–991 (1995).

    CAS  PubMed  Google Scholar 

  98. Kirchhoff, F., Greenough, T.C., Brettler, D.B., Sullivan, J.L. & Desrosiers, R.C. Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N. Engl. J. Med. 332, 228–232 (1995).

    CAS  PubMed  Google Scholar 

  99. Huang, Y. et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat. Med. 2, 1240–3 (1996).

    CAS  PubMed  Google Scholar 

  100. Lifson, J.D. et al. Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature 323, 725–728 (1986).

    CAS  PubMed  Google Scholar 

  101. Sodroski, J., Goh, W.C., Rosen, C., Campbell, K. & Haseltine, W.A. Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. Nature 322, 470–474 (1986).

    CAS  PubMed  Google Scholar 

  102. LaBonte, J.A., Patel, T., Hofmann, W. & Sodroski, J. Importance of membrane fusion mediated by human immunodeficiency virus envelope glycoproteins for lysis of primary CD4-positive T cells. J. Virol. 74, 10690–10698 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Etemad-Moghadam, B. et al. Membrane-fusing capacity of the human immunodeficiency virus envelope proteins determines the efficiency of CD4+ T cell depletion in macaques infected by a simian-human immunodeficiency virus. J. Virol. 75, 5646–5655 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Stewart, S.A., Poon, B., Jowett, J.B.M. & Chen, I.S.Y. Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest. J. Virol. 71, 5579–5592 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Somasundaran, M. et al. Evidence for a cytopathogenicity determinant in HIV-1 Vpr. Proc. Natl. Acad. Sci. USA 99, 9503–9508 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Asjo, B. et al. Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet 2, 660–662 (1986).

    CAS  PubMed  Google Scholar 

  107. Cheng-Mayer, C., Seto, D., Tateno, M. & Levy, J.A. Biologic features of HIV-1 that correlate with virulence in the host. Science 240, 80–82 (1988).

    CAS  PubMed  Google Scholar 

  108. Tersmette, M. et al. Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J. Virol. 62, 2026–2032 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Connor, R.I., Sheridan, K.E., Ceradini, D., Choe, S. & Landau, N.R. Change in coreceptor use coreceptor use correlates with disease progression in HIV-1–infected individuals. J. Exp. Med. 185, 621–628 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Meyaard, L. et al. Programmed death of T cells in HIV-1 infection. Science 257, 217–219 (1992).

    CAS  PubMed  Google Scholar 

  111. Finkel, T.H. et al. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes. Nat. Med. 1, 129–134 (1995).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  113. Wolthers, K.C. et al. T cell telomere length in HIV-1 infection: no evidence for increased CD4+ T cell turnover. Science 274, 1543–1546 (1996).

    CAS  PubMed  Google Scholar 

  114. Hellerstein, M. et al. Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans. Nat. Med. 5, 83–89 (1999).

    CAS  PubMed  Google Scholar 

  115. Kovacs, J.A. et al. Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV. J. Exp. Med. 194, 1731–1741 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Grossman, Z., Meier-Schellersheim, M., Sousa, A.E., Victorino, R.M. & Paul, W.E. CD4+ T cell depletion in HIV infection: are we closer to understanding the cause? Nat. Med. 8, 319–323 (2002).

    CAS  PubMed  Google Scholar 

  117. Douek, D.C. et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 396, 690–695 (1998).

    CAS  PubMed  Google Scholar 

  118. Letvin, N.L. et al. Induction of AIDS-like disease in macaque monkeys with T cell tropic retrovirus STLV-III. Science 230, 71–73 (1985).

    CAS  PubMed  Google Scholar 

  119. 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 

  120. Silvestri, G. et al. Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity 18, 441–452 (2003).

    CAS  PubMed  Google Scholar 

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Acknowledgements

Space limitations prevent the citation of many important sources of data discussed in this review. I thank N. Nelson for assistance with manuscript preparation and acknowledge the National Institutes of Health and the Jenner Foundation for research support.

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    Mario Stevenson

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Stevenson, M. HIV-1 pathogenesis. Nat Med 9, 853–860 (2003). https://doi.org/10.1038/nm0703-853

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