Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Targeting early infection to prevent HIV-1 mucosal transmission

Abstract

Measures to prevent sexual mucosal transmission of human immunodeficiency virus (HIV)-1 are urgently needed to curb the growth of the acquired immunodeficiency syndrome (AIDS) pandemic and ultimately bring it to an end. Studies in animal models and acute HIV-1 infection reviewed here reveal potential viral vulnerabilities at the mucosal portal of entry in the earliest stages of infection that might be most effectively targeted by vaccines and microbicides, thereby preventing acquisition and averting systemic infection, CD4 T-cell depletion and pathologies that otherwise rapidly ensue.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Time frame, sites and major events in vaginal transmission and the fast phase of lentivirus infection.
Figure 2: Ill effects of systemic infection and too little too late immune response.
Figure 3: Inflammation, innate immunity, mucosal epithelial signalling and target cell availability at mucosal front lines.

Similar content being viewed by others

References

  1. UNAIDS. 2008 Report on the global AIDS epidemic 〈http://www.unaids.org/en/KnowledgeCentre/HIVData/GlobalReport/2008/2008_Global_report.asp〉 (2008)

  2. Fauci, A. S. 25 years of HIV. Nature 453, 289–290 (2008)

    ADS  CAS  PubMed  Google Scholar 

  3. Cohen, J. Treatment and prevention exchange vows at international conference. Science 321, 902–903 (2008)

    CAS  PubMed  Google Scholar 

  4. 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)

    PubMed  Google Scholar 

  5. 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)

    PubMed  PubMed Central  Google Scholar 

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

    PubMed  Google Scholar 

  7. 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)

    CAS  PubMed  Google Scholar 

  8. Karim, S. A. et al. Safety and effectiveness of vaginal microbicides BufferGel and 0.5% PRO 2000/5 gel for the prevention of HIV infection in women: Results of the HPTN 035 trial. Abstract 48LB (16th Conference on Retroviruses and Opportunistic Infections, 2009)

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

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Check, E. Scientists rethink approach to HIV gels. Nature 446, 12 (2007)

    ADS  PubMed  Google Scholar 

  11. Fauci, A. et al. HIV vaccine research: the way forward. Science 321, 530–532 (2008)

    ADS  CAS  PubMed  Google Scholar 

  12. Quinn, T. C. & Overbaugh, J. HIV/AIDS in women: an expanding epidemic. Science 308, 1582–1583 (2005)

    ADS  CAS  PubMed  Google Scholar 

  13. Haase, A. The slow infection caused by visna virus. Curr. Top. Microbiol. Immunol. 72, 101–156 (1975)

    CAS  PubMed  Google Scholar 

  14. Miller, C. J. et al. Genital mucosal transmission of simian immunodeficiency virus: animal model for heterosexual transmission of human immunodeficiency virus. J. Virol. 63, 4277–4284 (1989)

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Fiebig, E. W. et al. Dynamics of HIV viremia and seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 17, 1871–1879 (2003)

    PubMed  Google Scholar 

  16. Miller, C. J. et al. Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J. Virol. 79, 9217–9227 (2005)Comprehensive tissue analysis of the pathogenesis of transmission and early infection in the nonhuman primate model of vaginal transmission of HIV-1.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Hu, J., Gardner, M. B. & Miller, C. J. Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J. Virol. 74, 6087–6095 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang, Z.-Q. et al. Sexual transmission and propagation of simian and human immunodeficiency viruses in two distinguishable populations of CD4+ T cells. Science 286, 1353–1357 (1999)First description of the CD4 T cell as the principal target in acute SIV and HIV-1 infections, and the surprising ostensibly resting phenotype of a majority of the CD4 T cells initially infected.

    CAS  PubMed  Google Scholar 

  19. Reinhart, T. et al. Simian immunodeficiency virus burden in tissues and cellular compartments during clinical latency and AIDS. J. Infect. Dis. 176, 1198–1208 (1997)

    CAS  PubMed  Google Scholar 

  20. Haase, A. T. Population biology of HIV-1 infection: viral and CD4+ T cell demographics and dynamics in lymphatic tissues. Annu. Rev. Immunol. 17, 625–656 (1999)

    CAS  PubMed  Google Scholar 

  21. Miller, C. M. & Shattock, R. J. Target cells in vaginal HIV transmission. Microbes Infect. 5, 59–67 (2003)

    CAS  PubMed  Google Scholar 

  22. Christopher, D. P. et al. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J. Infect. Dis. 189, 1785–1792 (2004)

    Google Scholar 

  23. Keele, B. F. et al. Low-dose rectal inoculation of rhesus macaques by SIV smE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J. Exp. Med. 206, 1117–1134 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Sodora, D. L., Gettie, A., Miller, C. J. & Marx, P. A. Vaginal transmission of SIV: assessing infectivity and hormonal influences in macaques inoculated with cell-free and cell-associated viral stocks. AIDS Res. Hum. Retroviruses 14 (Suppl. 1). S119–S123 (1998)

    PubMed  Google Scholar 

  25. Weiler, A. M. et al. Genital ulcers facilitate rapid viral entry and dissemination following intravaginal inoculation with cell-associated simian immunodeficiency virus SIVmac239. J. Virol. 82, 4154–4158 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Miyake, A. et al. Rapid dissemination of a pathogenic simian/human immunodeficiency virus to systemic organs and active replication in lymphoid tissues following intrarectal infection. J. Gen. Virol. 87, 1311–1320 (2006)

    CAS  PubMed  Google Scholar 

  27. Stahl-Hennig, C. et al. Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus. Science 285, 1261–1265 (1999)

    CAS  PubMed  Google Scholar 

  28. Milush, J. M. et al. Rapid dissemination of SIV following oral inoculation. AIDS 18, 1–10 (2004)

    Google Scholar 

  29. 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)

    ADS  CAS  PubMed  Google Scholar 

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

    ADS  CAS  PubMed  Google Scholar 

  31. Li, Q. et al. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 434, 1148–1152 (2005)Tissue analysis that revealed the rapid kinetics of acute SIV infection after vaginal exposure, predominance of productive infection in resting memory CD4 T cells, and the loss of gut lamina propria CD4 T cells mediated mainly by apoptosis.

    ADS  CAS  PubMed  Google Scholar 

  32. Clayton, F., Snow, G., Reka, S. & Kotler, D. P. Selective depletion of rectal lamina propria rather than lymphoid aggregate CD4 lymphocytes in HIV infection. Clin. Exp. Immunol. 107, 288–292 (1997)

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 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)

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 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)

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Guadalupe, M. et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J. Virol. 77, 11708–11717 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Kotler, D. P., Gaetz, H. P., Lange, M., Klein, E. B. & Holt, P. R. Enteropathy associated with the acquired immunodeficiency syndrome. Ann. Intern. Med. 101, 421–428 (1984)

    CAS  PubMed  Google Scholar 

  37. Heise, C., Miller, C. J., Lackner, A. & Dandekar, S. Primary acute simian immunodeficiency virus infection of intestinal lymphoid tissue is associated with gastrointestinal dysfunction. J. Infect. Dis. 169, 1116–1120 (1994)

    CAS  PubMed  Google Scholar 

  38. Li, Q. et al. Simian immunodeficiency virus-induced intestinal cell apoptosis is the underlying mechanism of the regenerative enteropathy of early infection. J. Infect. Dis. 197, 420–429 (2008)

    PubMed  Google Scholar 

  39. Estes, J. D. et al. Premature induction of an immunosuppressive T regulatory response in acute SIV infection. J. Infect. Dis. 193, 703–712 (2006)

    CAS  PubMed  Google Scholar 

  40. Reynolds, M. R. et al. The CD8+ T-lymphocyte response to major immunodominant epitopes after vaginal exposure to SIV: too late and too little. J. Virol. 79, 9228–9235 (2005)Comprehensive tissue analysis after vaginal exposure that revealed the ‘too late and too little’ CD8 T-cell response to prevent massive gut CD4 T-cell depletion in acute SIV infection but a robust response in cervical vaginal tissues that could potentially prevent acquisition if elicited earlier by a vaccine.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  42. Estes, J. D. et al. Simian immunodeficiency virus-induced lymphatic tissue fibrosis is mediated by transforming growth factor β1-positive regulatory T cells and begins in early infection. J. Infect. Dis. 195, 551–561 (2007)

    CAS  PubMed  Google Scholar 

  43. Estes, J. D., Haase, A. T. & Schacker, T. W. The role of collagen deposition in depleting CD4+ T cells and limiting reconstitution of HIV-1 and SIV infections through damage to the secondary lymphoid organ niche. Semin. Immunol. 20, 181–186 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Wolinsky, S. et al. Selective transmission of human deficiency virus type 1 variants from mothers to infants. Science 255, 1134–1137 (1992)

    ADS  CAS  PubMed  Google Scholar 

  45. Zhu, T. et al. 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, 3098–3107 (1996)

    MathSciNet  CAS  PubMed  PubMed Central  Google Scholar 

  46. Derdeyn, C. A. et al. Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science 303, 2019–2022 (2004)First description of the monophyletic nature of viruses transmitted heterosexually.

    ADS  CAS  PubMed  Google Scholar 

  47. Keele, B. F. et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc. Natl Acad. Sci. USA 105, 7552–7557 (2008)Comprehensive sequence analysis showing that a single virus genotype initiates the vast majority of HIV-1 infections.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  48. Salazar-Gonzalez, J. F. et al. Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. J. Exp. Med. 206, 1273–1289 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Norvell, M. K., Benrubi, G. I. & Thompson, R. J. Investigation of microtrauma after sexual intercourse. J. Reprod. Med. 269, 269–271 (1984)

    Google Scholar 

  50. Pudney, J., Quayle, A. J. & Anderson, D. J. Immunological microenvironments in the human vagina and cervix: mediators of cellular immunity are concentrated in the cervical transformation zone. Biol. Reprod. 73, 1253–1263 (2005)

    CAS  PubMed  Google Scholar 

  51. O’Connor, D. M. A tissue basis for colposcopic findings. Obstet. Gynecol. Clin. North Am. 35, 565–582 (2008)

    PubMed  Google Scholar 

  52. Li, Q. et al. Glycerol monolaurate prevents mucosal SIV transmission. Nature 458, 1034–1038 (2009)Tissue analysis of vaginal transmission revealing local expansion of small, infected founder populations, in vivo evidence of mucosal epithelial signalling that elicited an inflammatory response to fuel local expansion, and the ability of glycerol monolaurate to prevent transmission potentially by blocking signalling at mucosal front lines.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  53. Myer, L., Wright, T. C., Denny, L. & Kuhn, L. Nested case-control study of cervical mucosal lesions ectopy, and incident HIV infection among women in Cape Town, South Africa. Sex. Transm. Dis. 33, 683–687 (2006)

    PubMed  Google Scholar 

  54. Miller, C. J., Alexander, N. J., Vogel, P., Anderson, J. & Marx, P. A. Mechanism of genital transmission of SIV: a hypothesis based on transmission studies and location of SIV in the genital tract of chronically infected female rhesus macaques. J. Med. Primatol. 21, 64–68 (1992)

    CAS  PubMed  Google Scholar 

  55. Kell, P. D., Barton, S. E., Edmonds, D. K. & Boag, F. C. HIV infection in a patient with Meyer-Rokitansky-Kuster-Hauser syndrome. J. R. Soc. Med. 85, 706–707 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Padian, N. S. et al. Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomised controlled trial. Lancet 370, 251–261 (2007)

    PubMed  PubMed Central  Google Scholar 

  57. Berger, E. A., Murphy, P. M. & Farber, J. M. Chemokine receptors as HIV-1 coreceptors: Roles in viral entry, tropism, and disease. Annu. Rev. Immunol. 17, 657–700 (1999)

    CAS  PubMed  Google Scholar 

  58. Arthos, J. et al. HIV-1 envelope binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells. Nature Immunol. 9, 301–309 (2008)

    CAS  Google Scholar 

  59. Kader, M. et al. α4β7hiCD4+ memory T cells harbor most TH -17 cells and are preferentially infected during acute SIV infection. Mucosal Immunol. 2, 439–449 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Zhang, Z.-Q. et al. Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection. Proc. Natl Acad. Sci. USA 101, 5640–5645 (2004)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  61. Schacker, T. S. et al. Productive infection of T cells in lymphoid tissues during primary and early human immunodeficiency virus infection. J. Infect. Dis. 183, 555–562 (2001)

    CAS  PubMed  Google Scholar 

  62. Ma, Z., Lü, F. X., Torten, M. & Miller, C. J. The number and distribution of immune cells in the cervicovaginal mucosa remain constant throughout the menstrual cycle of rhesus macaques. Clin. Immunol. 100, 240–249 (2001)

    CAS  PubMed  Google Scholar 

  63. Edwards, J. N. T. & Morris, H. B. Langerhans’ cells and lymphocyte subsets in the female genital tract. Br. J. Obstet. Gynaecol. 92, 974–982 (1985)

    CAS  PubMed  Google Scholar 

  64. Wira, C. R., Fahey, J. V., Sentman, C. L., Pioli, P. A. & Shen, L. Innate and adaptive immunity in female genital tract: cellular responses and interactions. Immunol. Rev. 206, 306–335 (2005)

    PubMed  Google Scholar 

  65. Wira, C. R., Grant-Tschudy, K. S. & Crane-Godreau, M. A. Epithelial cells in the female reproductive tract: a central role as sentinels of immune protection. Am. J. Reprod. Immunol. 53, 65–76 (2005)

    CAS  PubMed  Google Scholar 

  66. Fahey, J. V. et al. Estradiol selectively regulates innate immune function by polarized human uterine epithelial cells in culture. Mucosal Immunol. 1, 317–325 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Dieu-nosjean, M. et al. Macrophage inflammatory protein 3α is expressed at inflamed epithelial surfaces and is the most potent chemokine known in attracting Langerhans cell precursors. J. Exp. Med. 192, 705–717 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Cremel, M. et al. Characterization of CCL20 secretion by human epithelial vaginal cells: involvement in Langerhans cell precursor attraction. J. Leukoc. Biol. 78, 158–166 (2005)

    CAS  PubMed  Google Scholar 

  69. Abel, K., Rocke, D. M., Chohan, B., Fritts, L. & Miller, C. J. Temporal and anatomic relationship between virus replication and cytokine gene expression after vaginal simian immunodeficiency virus infection. J. Virol. 79, 12164–12172 (2005)

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Gray, R. H. et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 357, 1149–1153 (2001)

    CAS  PubMed  Google Scholar 

  71. Wawer, M. J. et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J. Infect. Dis. 191, 1403–1409 (2005)

    PubMed  Google Scholar 

  72. Vendrame, D., Sourisseau, M., Perrin, V., Schwartz, O. & Mamano, F. Partial inhibition of human immunodeficiency virus replication by type I interferons: Impact of cell-to-cell viral transfer. J. Virol. 83, 10527–10537 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Rudnicka, D. et al. Simultaneous cell-to-cell transmission of human immunodeficiency virus to multiple targets through polysynapses. J. Virol. 83, 6234–6246 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Wang, Y. et al. The toll-like receptor 7 (TLR7) agonist, imiquimod and the TLR9 agonist, CpG ODN, induce antiviral cytokines and chemokines but do not prevent vaginal transmission of simian immunodeficiency virus when applied intravaginally to rhesus macaques. J. Virol. 79, 14355–14370 (2005)

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Glavin, S. R. & Cohen, M. S. The role of sexually transmitted diseases in HIV transmission. Nature Rev. Microbiol. 2, 33–42 (2004)

    Google Scholar 

  76. Kaul, R. et al. The genital tract immune milieu: an important determinant of HIV susceptibility and secondary transmission. J. Reprod. Immunol. 77, 32–40 (2008)

    CAS  PubMed  Google Scholar 

  77. Haaland, R. E. et al. Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1. PLoS Pathog. 5, 1–13 (2009)

    Google Scholar 

  78. Celum, C. et al. Effect of acyclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomized, double-blind, placebo-controlled trial. Lancet 371, 2109–2119 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Watson-Jones, D. et al. Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. N. Engl. J. Med. 358, 1560–1571 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Zhu, J. et al. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nature Med. 15, 886–893 (2009)Report of persistent target cells in healed HSV-2 ulcers after acyclovir treatment as the potential explanation for the failure of treatment to reduce HIV-1 acquisition.

    CAS  PubMed  Google Scholar 

  81. Robertson, S. A. Seminal plasma and male factor signalling in the female reproductive tract. Cell Tissue Res. 322, 43–52 (2005)

    PubMed  Google Scholar 

  82. Robertson, S. A., Ingman, W. V., O’Leary, S., Sharkey, D. J. & Tremellen, K. P. Transforming growth factor β—a mediator of immune deviation in seminal plasma. J. Reprod. Immunol. 57, 109–128 (2002)

    CAS  PubMed  Google Scholar 

  83. Berlier, W. et al. Seminal plasma promotes the attraction of Langerhans cells via the secretion of CCL20 by vaginal epithelial cells: involvement in the sexual transmission of HIV. Hum. Reprod. 21, 1135–1142 (2006)

    CAS  PubMed  Google Scholar 

  84. Münch, J. et al. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell 131, 1059–1071 (2007)

    PubMed  Google Scholar 

  85. Li, Q. et al. Visualizing antigen-specific and infected cells in situ predicts outcomes in early viral infection. Science 323, 1726–1729 (2009)Report of the tissue-compartment-specific nature of the cellular immune response that reveals the importance of the relative numbers of both immune effectors and infected targets in determining whether viral infection is cleared, and the extent of control if infection is not cleared.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  86. Belyakov, I. M. et al. Impact of vaccine-induced mucosal high-avidity CD8+ CTLs in delay of AIDS viral dissemination from mucosa. Blood 107, 3258–3264 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Genescà, M., Skinner, P. J., Bost, K. M., Lu, D. & Wang, Y. Protective attenuated lentivirus immunization induces SIV-specific T cells in the genital tract of rhesus monkeys. Mucosal Immunol. 1, 219–228 (2008)

    PubMed  PubMed Central  Google Scholar 

  88. Hansen, S. G. et al. Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nature Med. 15, 293–299 (2009)Report of impressive protection against rectal transmission associated with effector memory T-cell responses elicited by a rhesus CMV vaccine.

    CAS  PubMed  Google Scholar 

  89. Lifson, J. D. et al. Containment of simian immunodeficiency virus infection: Cellular immune responses and protection from rechallenge following transient postinoculation antiretroviral treatment. J. Virol. 74, 2584–2593 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Veazey, R. S. et al. Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion. Nature 438, 99–102 (2005)

    ADS  CAS  PubMed  Google Scholar 

  91. Lederman, M. M. et al. Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5. Science 306, 485–487 (2004)

    ADS  CAS  PubMed  Google Scholar 

  92. Cranage, M. et al. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel. PLoS Med. 5, 1238–1250 (2008)

    CAS  Google Scholar 

  93. Zhu, T. et al. Persistence of extraordinarily low levels of genetically homogeneous human immunodeficiency virus type 1 in exposed seronegative individuals. J. Virol. 77, 6108–6116 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  94. McChesney, M. B. et al. Occult systemic infection and persistent simian immunodeficiency virus (SIV)-specific CD4+-T-cell proliferative responses in rhesus macaques that were transiently viremic after intravaginal inoculation of SIV. J. Virol. 72, 10029–10035 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Ma, Z.-M., Abel, K., Rourke, T., Wang, Y. & Miller, C. J. A period of transient viremia and occult infection precedes persistent viremia and antiviral immune responses during multiple low-dose intravaginal simian immunodeficiency virus inoculations. J. Virol. 78, 14048–14052 (2004)

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Trivedi, P. et al. Intrarectal transmission of simian immunodeficiency virus in rhesus macaques: selective amplification and host responses to transient or persistent viremia. J. Virol. 70, 6876–6883 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Li, Q. et al. Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection. J. Immunol. 183, 1975–1982 (2009)

    CAS  PubMed  Google Scholar 

  98. Virgin, H. W. & Walker, B. D. Immunology and the elusive AIDS vaccine. Nature (in the press)

Download references

Acknowledgements

I thank J. V. Carlis, R. P. Johnson, Q. Li, J. D. Lifson, D. Masopust, S. Pambuccian, P. J. Southern, J. Estes, D. Douek, H. W. Virgin and B. D. Walker for discussions. Errors of commission are mine as are errors of omission, with apologies to the authors of work that I could not cite because of space limitations and exclusive focus on tissue analyses. I thank C. O’Neill and T. Leonard for help with the manuscript and figures. Work from my laboratory cited in the review was supported by grants from the National Institutes of Health (AI 38565, AI 48484, AI 71976) and the International AIDS Vaccine Initiative.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ashley T. Haase.

Ethics declarations

Competing interests

The author declares no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haase, A. Targeting early infection to prevent HIV-1 mucosal transmission. Nature 464, 217–223 (2010). https://doi.org/10.1038/nature08757

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature08757

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing