About this Journal Submit a Manuscript Table of Contents
Clinical and Developmental Immunology
Volume 2012 (2012), Article ID 875821, 10 pages
http://dx.doi.org/10.1155/2012/875821
Review Article

Natural Immunity to HIV: A Delicate Balance between Strength and Control

Laboratoire d’Immunogénétique, Centre de Recherche, Centre Hospitalier de l’Université de Montréal (CRCHUM) et Département de Microbiologie et Immunologie, Université de Montréal, Montreal, QC, Canada H2L 4M1

Received 14 August 2012; Revised 10 November 2012; Accepted 16 November 2012

Academic Editor: Vicki L. Traina-Dorge

Copyright © 2012 Johanne Poudrier et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. http://www.unaids.org/globalreport/Global_report.htm.
  2. J. J. Schellenberg and F. A. Plummer, “The microbiological context of HIV resistance: vaginal microbiota and mucosal inflammation at the viral point of entry,” International Journal of Inflammation, vol. 2012, Article ID 131243, 10 pages, 2012. View at Publisher · View at Google Scholar
  3. S. Moir and A. S. Fauci, “B cells in HIV infection and disease,” Nature Reviews Immunology, vol. 9, no. 4, pp. 235–245, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Bomsel, D. Tudor, A. S. Drillet et al., “Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges,” Immunity, vol. 34, no. 2, pp. 269–280, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. M. J. McElrath, “Standing guard at the mucosa,” Immunity, vol. 34, no. 2, pp. 146–148, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. G. D. Tomaras and B. F. Haynes, “Strategies for eliciting HIV-1 inhibitory antibodies,” Current Opinion in HIV and AIDS, vol. 5, no. 5, pp. 421–427, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. B. F. Haynes, P. B. Gilbert, M. J. McElrath, et al., “Immune-correlates analysis of an HIV vaccine efficacy trial,” The New England Journal of Medicine, pp. 1275–1286, 2012.
  8. F. Hladik and M. J. McElrath, “Setting the stage: host invasion by HIV,” Nature Reviews Immunology, vol. 8, no. 6, pp. 447–457, 2008. View at Publisher · View at Google Scholar · View at Scopus
  9. A. T. Haase, “Early events in sexual transmission of hiv and siv and opportunities for interventions,” Annual Review of Medicine, vol. 62, pp. 127–139, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. D. K. Hickey, M. V. Patel, J. V. Fahey, and C. R. Wira, “Innate and adaptive immunity at mucosal surfaces of the female reproductive tract: stratification and integration of immune protection against the transmission of sexually transmitted infections,” Journal of Reproductive Immunology, vol. 88, no. 2, pp. 185–194, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. A. J. Quayle, “The innate and early immune response to pathogen challenge in the female genital tract and the pivotal role of epithelial cells,” Journal of Reproductive Immunology, vol. 57, no. 1-2, pp. 61–79, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. A. W. Horne, S. J. Stock, and A. E. King, “Innate immunity and disorders of the female reproductive tract,” Reproduction, vol. 135, no. 6, pp. 739–749, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. R. T. Triforiova, G. F. Doncel, and R. N. Fichorova, “Polyanionic microbicides modify toll-like receptor-mediated cervicovaginal immune responses7,” Antimicrobial Agents and Chemotherapy, vol. 53, no. 4, pp. 1490–1500, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. S. C. Gribar, W. M. Richardson, C. P. Sodhi, and D. J. Hackam, “No longer an innocent bystander: epithelial toll-like receptor signaling in the development of mucosal inflammation,” Molecular Medicine, vol. 14, no. 9-10, pp. 645–659, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. J. Den Dunnen, S. I. Gringhuis, and T. B. H. Geijtenbeek, “Innate signaling by the C-type lectin DC-SIGN dictates immune responses,” Cancer Immunology, Immunotherapy, vol. 58, no. 7, pp. 1149–1157, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. P. Pala, V. R. Gomez-Roman, J. Gilmour, and P. Kaleebu, “An African perspective on mucosal immunity and HIV-1,” Mucosal Immunology, vol. 2, no. 4, pp. 300–314, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. B. L. Shacklett, “Immune responses to HIV and SIV in mucosal tissues: ‘location, location, location’,” Current Opinion in HIV and AIDS, vol. 5, no. 2, pp. 128–134, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. A. Cerutti, I. Puga, and M. Cols, “Innate control of B cell responses,” Trends in Immunology, vol. 32, no. 5, pp. 202–211, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. R. G. Gaudet, F. Breden, F. Plummer, and J. D. Berry, “Molecular characterization of the cervical and systemic B-cell repertoire: unique, yet overlapping, immune compartments of an HIV-1 resistant individual,” mAbs, vol. 3, no. 2, pp. 184–194, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. N. Derby, E. Martinelli, and M. Robbiani, “Myeloid dendritic cells in HIV-1 infection,” Current Opinion in HIV and AIDS, vol. 6, pp. 379–384, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. M. van der Vlist, A. M. G. van der Aar, S. I. Gringhuis, and T. B. H. Geijtenbeek, “Innate signaling in HIV-1 infection of dendritic cells,” Current Opinion in HIV and AIDS, vol. 6, pp. 348–352, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. A. Smed-Sörensen and K. Loré, “Dendritic cells at the interface of innate and adaptive immunity to HIV-1,” Current Opinion in HIV and AIDS, vol. 6, pp. 405–410, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. F. Blanchet, A. Moris, J. P. Mitchell, and V. Piguet, “A look at HIV journey: from dendritic cells to infection spread in CD4+ T cells,” Current Opinion in HIV and AIDS, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. Q. Li, J. D. Estes, P. M. Schlievert et al., “Glycerol monolaurate prevents mucosal SIV transmission,” Nature, vol. 458, no. 7241, pp. 1034–1038, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Bouschbacher, M. Bomsel, E. Verronèse et al., “Early events in HIV transmission through a human reconstructed vaginal mucosa,” AIDS, vol. 22, no. 11, pp. 1257–1266, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. C. H. Fox, D. Kotler, A. Tierney, C. S. Wilson, and A. S. Fauci, “Detection of HIV-1 RNA in the lamina propria of patients with AIDS and gastrointestinal disease,” Journal of Infectious Diseases, vol. 159, no. 3, pp. 467–471, 1989. View at Scopus
  27. S. N. Asin, M. W. Fanger, D. Wildt-Perinic, P. L. Ware, C. R. Wira, and A. L. Howell, “Transmission of HIV-1 by primary human uterine epithelial cells and stromal fibroblasts,” Journal of Infectious Diseases, vol. 190, no. 2, pp. 236–245, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. H. Hocini, P. Becquart, H. Bouhlal et al., “Active and selective transcytosis of cell-free human immunodeficiency virus through a tight polarized monolayer of human endometrial cells,” Journal of Virology, vol. 75, no. 11, pp. 5370–5374, 2001. View at Publisher · View at Google Scholar · View at Scopus
  29. C. S. Dezzutti, P. C. Guenthner, J. E. Cummins et al., “Cervical and prostate primary epithelial cells are not productively infected but sequester human immunodeficiency virus type 1,” Journal of Infectious Diseases, vol. 183, no. 8, pp. 1204–1213, 2001. View at Publisher · View at Google Scholar · View at Scopus
  30. Z. Wu, Z. Chen, and D. M. Phillips, “Human genital epithelial cells capture cell-free human immunodeficiency virus type 1 and transmit the virus to CD4+ cells: implications for mechanisms of sexual transmission,” Journal of Infectious Diseases, vol. 188, no. 10, pp. 1473–1482, 2003. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Nazli, O. Chan, W. N. Dobson-Belaire et al., “Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation,” PLoS Pathogens, vol. 6, no. 4, Article ID e1000852, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. D. Fontenot, H. He, S. Hanabuchi et al., “TSLP production by epithelial cells exposed to immunodeficiency virus triggers DC-mediated mucosal infection of CD4+ T cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 39, pp. 16776–16781, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. D. Fontenot, The role of mucosal epithelial cells in HIV infection [Dissertations and Theses], UT Graduate School of Biomedical Sciences at Houston, 2010, http://digitalcommons.library.tmc.edu/utgsbs_dissertations/28.
  34. H. Yu, D. Tudor, A. Alfsen, B. Labrosse, F. Clavel, and M. Bomsel, “Peptide P5 (residues 628–683), comprising the entire membrane proximal region of HIV-1 gp41 and its calcium-binding site, is a potent inhibitor of HIV-1 infection,” Retrovirology, vol. 5, article 93, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. L. R. McKinnon and R. Kaul, “Quality and quantity: mucosal CD4+ T cells and HIV susceptibility,” Current Opinion in HIV and AIDS, vol. 7, no. 2, pp. 195–202, 2012. View at Publisher · View at Google Scholar
  36. L. R. McKinnon, B. Nyanga, D. Chege, et al., “Characterization of a human cervical CD4 + T cell subset coexpressing multiple markers of HIV susceptibility,” Journal of Immunology, vol. 187, no. 11, pp. 6032–6042, 2011. View at Publisher · View at Google Scholar
  37. A. Gosselin, P. Monteiro, N. Chomont et al., “Peripheral blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T cells are highly permissive to HIV-1 infection,” Journal of Immunology, vol. 184, no. 3, pp. 1604–1616, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. P. Monteiro, A. Gosselin, V. S. Wacleche et al., “Memory CCR6+CD4+ T cells are preferential targets for productive HIV type 1 infection regardless of their expression of integrin β7,” Journal of Immunology, vol. 186, no. 8, pp. 4618–4630, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. M. Kader, X. Wang, M. Piatak et al., “α4+β7hiCD4+ memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection,” Mucosal Immunology, vol. 2, no. 5, pp. 439–449, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. J. M. Brenchley, M. Paiardini, K. S. Knox et al., “Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections,” Blood, vol. 112, no. 7, pp. 2826–2835, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. D. Favre, S. Lederer, B. Kanwar et al., “Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection,” PLoS Pathogens, vol. 5, no. 2, Article ID e1000295, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Arthos, C. Cicala, E. Martinelli et al., “HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells,” Nature Immunology, vol. 9, no. 3, pp. 301–309, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. N. Manel, D. Unutmaz, and D. R. Littman, “The differentiation of human TH-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt,” Nature Immunology, vol. 9, no. 6, pp. 641–649, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. E. Schutyser, S. Struyf, and J. Van Damme, “The CC chemokine CCL20 and its receptor CCR6,” Cytokine and Growth Factor Reviews, vol. 14, no. 5, pp. 409–426, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Cremel, W. Berlier, H. Hamzeh et al., “Characterization of CCL20 secretion by human epithelial vaginal cells: involvement in Langerhans cell precursor attraction,” Journal of Leukocyte Biology, vol. 78, no. 1, pp. 158–166, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. I. D. Iliev, E. Mileti, G. Matteoli, M. Chieppa, and M. Rescigno, “Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioning,” Mucosal Immunology, vol. 2, no. 4, pp. 340–350, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Rescigno and A. Di Sabatino, “Dendritic cells in intestinal homeostasis and disease,” The Journal of Clinical Investigation, vol. 119, no. 9, pp. 2441–2450, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. Q. Li, J. E. Agno, M. A. Edson, A. K. Nagaraja, T. Nagashima, and M. M. Matzuk, “Transforming growth factor β receptor type 1 is essential for female reproductive tract integrity and function,” PLoS Genetics, vol. 7, no. 10, Article ID e1002320, 2011. View at Publisher · View at Google Scholar
  49. D. J. Sharkey, A. M. Macpherson, K. P. Tremellen, D. G. Mottershead, R. B. Gilchrist, and S. A. Robertson, “TGF-β mediates proinflammatory seminal fluid signaling in human cervical epithelial cells,” Journal of Immunology, vol. 189, no. 2, pp. 1024–1035, 2012. View at Publisher · View at Google Scholar
  50. Y. Irnidayanti, “Effect of retinoic acid on fetus reproductive organ mice (Mus musculus) SwissWebster,” International Journal of Medical and Biological Sciences, vol. 6, pp. 223–225, 2012.
  51. L. Deng, G. L. Shipley, D. S. Loose-Mitchell et al., “Coordinate regulation of the production and signaling of retinoic acid by estrogen in the human endometrium,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 5, pp. 2157–2163, 2003. View at Publisher · View at Google Scholar · View at Scopus
  52. T. Takahashi, B. Eitzman, N. L. Bossert et al., “Transforming growth factors β1, β2, and β3 messenger RNA and protein expression in mouse uterus and vagina during estrogen-induced growth: a comparison to other estrogen-regulated genes,” Cell Growth and Differentiation, vol. 5, no. 9, pp. 919–935, 1994. View at Scopus
  53. R. T. Lester, X. D. Yao, T. B. Ball et al., “Toll-like receptor expression and responsiveness are increased in viraemic HIV-1 infection,” AIDS, vol. 22, no. 6, pp. 685–694, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. I. Pandrea, D. L. Sodora, G. Silvestri, and C. Apetrei, “Into the wild: simian immunodeficiency virus (SIV) infection in natural hosts,” Trends in Immunology, vol. 29, no. 9, pp. 419–428, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. J. M. Brenchley, D. A. Price, T. W. Schacker et al., “Microbial translocation is a cause of systemic immune activation in chronic HIV infection,” Nature Medicine, vol. 12, no. 12, pp. 1365–1371, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. J. N. Mandl, A. P. Barry, T. H. Vanderford et al., “Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections,” Nature Medicine, vol. 14, no. 10, pp. 1077–1087, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. S. H. Vermund, P. B. Tabereaux, and R. Kaslow, Textbook of AIDS Medicine, 1999.
  58. C. Tomescu, S. Abdulhaqq, and L. J. Montaner, “Evidence for the innate immune response as a correlate of protection in human immunodeficiency virus (HIV)-1 highly exposed seronegative subjects (HESN),” Clinical and Experimental Immunology, vol. 164, no. 2, pp. 158–169, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. S. Boulet, M. Kleyman, J. Y. Kim et al., “A combined genotype of KIR3DL1 high expressing alleles and HLA-B*57 is associated with a reduced risk of HIV infection,” AIDS, vol. 22, no. 12, pp. 1487–1491, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. W. Jennes, S. Verheyden, C. Demanet et al., “Cutting edge: resistance to HIV-1 infection among African female sex workers is associated with inhibitory KIR in the absence of their HLA ligands,” Journal of Immunology, vol. 177, no. 10, pp. 6588–6592, 2006. View at Scopus
  61. C. Matte, J. Lajoie, J. Lacaille, L. S. Zijenah, B. J. Ward, and M. Roger, “Functionally active HLA-G polymorphisms are associated with the risk of heterosexual HIV-1 infection in African women,” AIDS, vol. 18, no. 3, pp. 427–431, 2004. View at Publisher · View at Google Scholar · View at Scopus
  62. K. S. MacDonald, K. R. Fowke, J. Kimani et al., “Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection,” Journal of Infectious Diseases, vol. 181, no. 5, pp. 1581–1589, 2000. View at Publisher · View at Google Scholar · View at Scopus
  63. S. F. Lockett, J. R. Robertson, R. P. Brettle, P. L. Yap, D. Middleton, and A. J. L. Brown, “Mismatched human leukocyte antigen alleles protect against heterosexual HIV transmission,” Journal of Acquired Immune Deficiency Syndromes, vol. 27, no. 3, pp. 277–280, 2001. View at Scopus
  64. C. Liu, M. Carrington, R. A. Kaslow et al., “Association of polymorphisms in human leukocyte antigen class I and transporter associated with antigen processing genes with resistance to human immunodeficiency virus type 1 infection,” Journal of Infectious Diseases, vol. 187, no. 9, pp. 1404–1410, 2003. View at Publisher · View at Google Scholar · View at Scopus
  65. M. T. Dorak, J. Tang, A. Penman-Aguilar et al., “Transmission of HIV-1 and HLA-B allele-sharing within serodiscordant heterosexual Zambian couples,” The Lancet, vol. 363, no. 9427, pp. 2137–2139, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. T. B. Ball, H. Ji, J. Kimani et al., “Polymorphisms in IRF-1 associated with resistance to HIV-1 infection in highly exposed uninfected Kenyan sex workers,” AIDS, vol. 21, no. 9, pp. 1091–1101, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. P. Y. Bochud, M. Hersberger, P. Taffé et al., “Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection,” AIDS, vol. 21, no. 4, pp. 441–446, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Dean, M. Carrington, C. Winkler, et al., “Genetic restriction of HIV infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study,” Science, vol. 273, pp. 1856–1862.
  69. Y. Huang, W. A. Paxton, S. M. Wolinsky et al., “The role of a mutant CCR5 allele in HIV-1 transmission and disease progression,” Nature Medicine, vol. 2, no. 11, pp. 1240–1243, 1996. View at Publisher · View at Google Scholar · View at Scopus
  70. J. Eugen-Olsen, A. K. N. Iversen, P. Garred et al., “Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals,” AIDS, vol. 11, no. 3, pp. 305–310, 1997. View at Publisher · View at Google Scholar · View at Scopus
  71. A. M. De Roda Husman, M. Koot, M. Cornelissen et al., “Association between CCR5 genotype and the clinical course of HIV-1 infection,” Annals of Internal Medicine, vol. 127, no. 10, pp. 882–890, 1997. View at Scopus
  72. L. Meyer, M. Magierowska, J. B. Hubert et al., “Early protective effect of CCR-5 Δ32 heterozygosity on HIV-1 disease progression: relationship with viral load,” AIDS, vol. 11, no. 11, pp. F73–F78, 1997. View at Publisher · View at Google Scholar · View at Scopus
  73. P. A. Zimmerman, A. Buckler-White, G. Alkhatib et al., “Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5: studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk,” Molecular Medicine, vol. 3, no. 1, pp. 23–36, 1997. View at Scopus
  74. N. L. Michael, G. Chang, L. G. Louie et al., “The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression,” Nature Medicine, vol. 3, no. 3, pp. 338–340, 1997. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Misrahi, J. P. Teglas, N. N'Go et al., “CCR5 chemokine receptor variant in HIV-1 mother-to-child transmission and disease progression in children,” JAMA, vol. 279, no. 4, pp. 277–280, 1998. View at Publisher · View at Google Scholar · View at Scopus
  76. S. S. Bakshi, L. Zhang, D. Ho, S. Than, and S. G. Pahwa, “Distribution of CCR5δ32 in human immunodeficiency virus-infected children and its relationship to disease course,” Clinical and Diagnostic Laboratory Immunology, vol. 5, no. 1, pp. 38–40, 1998. View at Scopus
  77. M. W. Smith, M. Dean, M. Carrington, et al., “Contrasting genetic influence of CCR2 and CCR5 variants on HIV infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study,” Science, vol. 277, pp. 959–965, 1997.
  78. L. G. Kostrikis, Y. Huang, J. P. Moore et al., “A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation,” Nature Medicine, vol. 4, no. 3, pp. 350–353, 1998. View at Publisher · View at Google Scholar · View at Scopus
  79. E. Gonzalez, H. Kulkarni, H. Bolivar et al., “The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility,” Science, vol. 307, no. 5714, pp. 1434–1440, 2005. View at Publisher · View at Google Scholar · View at Scopus
  80. R. Colobran, P. Adreani, Y. Ashhab et al., “Multiple products derived from two CCL4 Loci: high incidence of a new polymorphism in HIV+ patients,” Journal of Immunology, vol. 174, no. 9, pp. 5655–5664, 2005. View at Scopus
  81. M. H. Malim and P. D. Bieniasz, “HIV restriction factors and mechanisms of evasion,” Cold Spring Harbour Perspectives in Medicine, vol. 2, no. 5, Article ID a006940, 2012.
  82. N. Laguette and M. Benkirane, “How Samhd1 changes our view of viral restriction,” Trends in Immunology, vol. 33, pp. 26–33, 2012.
  83. K. Mous, W. Jennes, M. Camara, et al., “Expression analysis of LEDGF/p75, APOBEC3G, TRIM5alpha, and tetherin in a Senegalese cohort of HIV-1-exposed seronegative individuals,” PLoS One, vol. 7, Article ID e33934, 2012. View at Publisher · View at Google Scholar
  84. M. Ghosh, Z. Shen, J. V. Fahey, S. Cu-Uvin, K. Mayer, and C. R. Wira, “Trappin-2/Elafin: a novel innate anti-human immunodeficiency virus-1 molecule of the human female reproductive tract,” Immunology, vol. 129, no. 2, pp. 207–219, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. M. Ghosh, J. V. Fahey, Z. Shen et al., “Anti-HIV activity in cervical-vaginal secretions from HIV-positive and -negative women correlate with innate antimicrobial levels and IgG antibodies,” PloS One, vol. 5, no. 6, Article ID e11366, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. A. G. Drannik, K. Nag, X.-D. Yao et al., “Anti-HIV-1 activity of elafin is more potent than its precursor's, trappin-2, in genital epithelial cells,” Journal of Virology, vol. 86, no. 8, pp. 4599–4610, 2012. View at Publisher · View at Google Scholar
  87. A. Burgener, S. Rahman, R. Ahmad et al., “Comprehensive proteomic study identifies serpin and cystatin antiproteases as novel correlates of HIV-1 resistance in the cervicovaginal mucosa of female Sex workers,” Journal of Proteome Research, vol. 10, no. 11, pp. 5139–5149, 2011. View at Publisher · View at Google Scholar
  88. S. L. Rowland-Jones, T. Dong, K. R. Fowke et al., “Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV- resistant prostitutes in Nairobi,” The Journal of Clinical Investigation, vol. 102, no. 9, pp. 1758–1765, 1998. View at Scopus
  89. R. Kaul, F. A. Plummer, J. Kimani et al., “HIV-1-specific mucosal CD8+ lymphocyte responses in the cervix of HIV- 1-resistant prostitutes in Nairobi,” Journal of Immunology, vol. 164, no. 3, pp. 1602–1611, 2000. View at Scopus
  90. R. Kaul, D. Trabattoni, J. J. Bwayo et al., “HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan sex workers,” AIDS, vol. 13, no. 1, pp. 23–29, 1999. View at Publisher · View at Google Scholar · View at Scopus
  91. K. R. Fowke, R. Kaul, K. L. Rosenthal et al., “HIV-1-specific cellular immune responses among HIV-1-resistant sex workers,” Immunology and Cell Biology, vol. 78, no. 6, pp. 586–595, 2000. View at Publisher · View at Google Scholar · View at Scopus
  92. S. M. Iqbal, T. B. Ball, J. Kimani et al., “Elevated T cell counts and RANTES expression in the genital mucosa of HIV-1-resistant Kenyan commercial sex workers,” Journal of Infectious Diseases, vol. 192, no. 5, pp. 728–738, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. J. B. Alimonti, S. A. Koesters, J. Kimani et al., “CD4+ T cell responses in HIV-exposed seronegative women are qualitatively distinct from those in HIV-infected women,” Journal of Infectious Diseases, vol. 191, no. 1, pp. 20–24, 2005. View at Publisher · View at Google Scholar · View at Scopus
  94. C. Devito, J. Hinkula, R. Kaul et al., “Cross-clade HIV-1-specific neutralizing IgA in mucosal and systemic compartments of HIV-1-exposed, persistently seronegative subjects,” Journal of Acquired Immune Deficiency Syndromes, vol. 30, no. 4, pp. 413–420, 2002. View at Scopus
  95. J. R. Almeida, D. A. Price, L. Papagno et al., “Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover,” Journal of Experimental Medicine, vol. 204, no. 10, pp. 2473–2485, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. M. R. Betts, M. C. Nason, S. M. West et al., “HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells,” Blood, vol. 107, no. 12, pp. 4781–4789, 2006. View at Publisher · View at Google Scholar · View at Scopus
  97. F. Pereyra, M. M. Addo, D. E. Kaufmann et al., “Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy,” Journal of Infectious Diseases, vol. 197, no. 4, pp. 563–571, 2008. View at Publisher · View at Google Scholar · View at Scopus
  98. L. Bélec, P. D. Ghys, H. Hocini et al., “Cervicovaginal secretory antibodies to human immunodeficiency virus type 1 (HIV-1) that block viral transcytosis through tight epithelial barriers in highly exposed HIV-1-seronegative African women,” Journal of Infectious Diseases, vol. 184, no. 11, pp. 1412–1422, 2001. View at Publisher · View at Google Scholar · View at Scopus
  99. H. Hocini and M. Bomsel, “Infectious human immunodeficiency virus can rapidly penetrate a tight human epithelial barrier by transcytosis in a process impaired by mucosal immunoglobulins,” Journal of Infectious Diseases, vol. 179, supplement 3, pp. S448–S453, 1999. View at Publisher · View at Google Scholar · View at Scopus
  100. J. Lajoie, J. Poudrier, M. Massinga-Loembe et al., “Differences in immunoregulatory cytokine expression patterns in the systemic and genital tract compartments of HIV-1-infected commercial sex workers in Benin,” Mucosal Immunology, vol. 1, no. 4, pp. 309–316, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. J. Lajoie, J. Poudrier, M. Massinga Loembe et al., “Chemokine expression patterns in the systemic and genital tract compartments are associated with HIV-1 infection in women from benin,” Journal of Clinical Immunology, vol. 30, no. 1, pp. 90–98, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. K. R. Fowke, N. J. D. Nagelkerke, J. Kimani et al., “Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya,” The Lancet, vol. 348, no. 9038, pp. 1347–1351, 1996. View at Publisher · View at Google Scholar · View at Scopus
  103. F. A. Plummer, T. B. Ball, J. Kimani, and K. R. Fowke, “Resistance to HIV-1 infection among highly exposed sex workers in Nairobi: what mediates protection and why does it develop?” Immunology Letters, vol. 66, no. 1–3, pp. 27–34, 1999. View at Publisher · View at Google Scholar · View at Scopus
  104. R. Kaul, S. L. Rowland-Jones, J. Kimani et al., “Late seroconversion in HIV-resistant Nairobi prostitutes despite pre-existing HIV-specific CD8+ responses,” The Journal of Clinical Investigation, vol. 107, no. 3, pp. 341–349, 2001. View at Scopus
  105. C. M. Card, P. J. McLaren, C. Wachihi, J. Kimani, F. A. Plummer, and K. R. Fowke, “Decreased immune activation in resistance to HIV-1 infection is associated with an elevated frequency of CD4+CD25+FOXP3+ Regulatory T Cells,” Journal of Infectious Diseases, vol. 199, no. 9, pp. 1318–1322, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. N. Ahmed, T. Hayashi, A. Hasegawa et al., “Suppression of human immunodeficiency virus type 1 replication in macrophages by commensal bacteria preferentially stimulating Toll-like receptor 4,” Journal of General Virology, vol. 91, no. 11, pp. 2804–2813, 2010. View at Publisher · View at Google Scholar · View at Scopus