Semen protects CD4+ target cells from HIV infection but promotes the preferential transmission of R5 tropic HIV

Journal of Immunology

Volumn 185, Issue 12, 2010, Pages 7596-7604

  Balandya, Emmanuel ^a   Sheth, Siddharth ^b   Sanders, Katherine ^b   Wieland Alter, Wendy ^c   Lahey, Timothy ^b,c,d  

^a Program in Experimental and Molecular Medicine   (United States)

^b Section of Infectious Diseases and International Health   (United States)

^c Department of Medicine ^*  (United States)

^d DARTMOUTH MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR4;

ARTICLE; CD4+ T LYMPHOCYTE; CELL PROTECTION; CELL SURFACE; CLINICAL ASSESSMENT; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LYMPHOCYTE ACTIVATION; LYMPHOCYTE PROLIFERATION; PRIORITY JOURNAL; SEMINAL PLASMA; SPERM; TARGET CELL; VIRUS TRANSMISSION;

CD4-POSITIVE T-LYMPHOCYTES; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, IMMUNOLOGIC; HIV INFECTIONS; HIV-1; HUMANS; LYMPHOCYTE ACTIVATION; MALE; SEMEN; TIME FACTORS;

EID: 78650675163     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1002846     Document Type: Article

References (60)

1. Granich, R. M., C. F. Gilks, C. Dye, K. M. De Cock, and B. G. Williams. 2009. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet 373:48-57.
2. Galvin, S. R., and M. S. Cohen. 2004. The role of sexually transmitted diseases in HIV transmission. Nat. Rev. Microbiol. 2:33-42.
3. Ball, J. K., R. Curran, W. L. Irving, and A. A. Dearden. 1999. HIV-1 in semen: determination of proviral and viral titres compared to blood, and quantification of semen leukocyte populations. J. Med. Virol. 59:356-363.
4. Butler, D. M., W. Delport, S. L. Kosakovsky Pond, M. K. Lakdawala, P. M. Cheng, S. J. Little, D. D. Richman, and D. M. Smith. 2010. The origins of sexually transmitted HIV among men who have sex with men. Sci. Transl. Med. 2:18re1.
5. Marcelin, A. G., R. Tubiana, S. Lambert-Niclot, G. Lefebvre, S. Dominguez, M. Bonmarchand, D. Vauthier-Brouzes, F. Marguet, N. Mousset-Simeon, G. Peytavin, and C. Poirot. 2008. Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma. AIDS 22:1677-1679.
6. Pilcher, C. D., G. Joaki, I. F. Hoffman, F. E. Martinson, C. Mapanje, P. W. Stewart, K. A. Powers, S. Galvin, D. Chilongozi, S. Gama, et al. 2007. Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection. AIDS 21:1723-1730.
7. Sheth, P. M., C. Kovacs, K. S. Kemal, R. B. Jones, J. M. Raboud, R. Pilon, C. la Porte, M. Ostrowski, M. Loutfy, H. Burger, et al; Toronto Mucosal Immunology Group. 2009. Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS 23:2050-2054.
8. Haase, A. T. 2010. Targeting early infection to prevent HIV-1 mucosal transmission. Nature 464:217-223.
9. Hladik, F., P. Sakchalathorn, L. Ballweber, G. Lentz, M. Fialkow, D. Eschenbach, and M. J. McElrath. 2007. Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity 26:257-270.
10. Pope, M., and A. T. Haase. 2003. Transmission, acute HIV-1 infection and the quest for strategies to prevent infection. Nat. Med. 9:847-852.
11. Shacklett, B. L. 2008. Mucosal immunity to HIV: a review of recent literature. Curr. Opin. HIV AIDS 3:541-547.
12. Wira, C. R., and J. V. Fahey. 2008. A new strategy to understand how HIV infects women: identification of a window of vulnerability during the menstrual cycle. AIDS 22:1909-1917.
13. Sabatté, J., A. Ceballos, S. Raiden, M. Vermeulen, K. Nahmod, J. Maggini, G. Salamone, H. Salomón, S. Amigorena, and J. Geffner. 2007. Human seminal plasma abrogates the capture and transmission of human immunodeficiency virus type 1 to CD4+ T cells mediated by DC-SIGN. J. Virol. 81:13723-13734.
14. Stax, M. J., T. van Montfort, R. R. Sprenger, M. Melchers, R. W. Sanders, E. van Leeuwen, S. Repping, G. Pollakis, D. Speijer, and W. A. Paxton. 2009. Mucin 6 in seminal plasma binds DC-SIGN and potently blocks dendritic cell mediated transfer of HIV-1 to CD4 (+) T-lymphocytes. Virology 391:203-211.
15. Martellini, J. A., A. L. Cole, N. Venkataraman, G. A. Quinn, P. Svoboda, B. K. Gangrade, J. Pohl, O. E. Sørensen, and A. M. Cole. 2009. Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma. FASEB J. 23:3609-3618.
16. Münch, J., E. Rücker, L. Ständker, K. Adermann, C. Goffinet, M. Schindler, S. Wildum, R. Chinnadurai, D. Rajan, A. Specht, et al. 2007. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell 131:1059-1071.
17. Ceballos, A., F. Remes Lenicov, J. Sabatté, C. Rodríguez Rodrígues, M. Cabrini, C. Jancic, S. Raiden, M. Donaldson, R. Agustín Pasqualini, Jr., C. Marin-Briggiler, et al. 2009. Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells. J. Exp. Med. 206:2717-2733.
18. Wolff, H. 1998. Methods for the detection of male genital tract inflammation. Andrologia 30 (Suppl 1):35-39.
19. Brown, W. F. 1964. Variance estimation in the Reed-Muench fifty per cent endpoint determination. Am. J. Hyg. 79:37-46.
20. Montefiori, D. C. 2009. Measuring HIV neutralization in a luciferase reporter gene assay. Methods Mol. Biol. 485:395-405.
21. Livak, K. J., and T. D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T)) method. Methods 25:402-408.
22. Cullen, B. R., and W. C. Greene. 1989. Regulatory pathways governing HIV-1 replication. Cell 58:423-426.
23. Douek, D. C., J. M. Brenchley, M. R. Betts, D. R. Ambrozak, B. J. Hill, Y. Okamoto, J. P. Casazza, J. Kuruppu, K. Kunstman, S. Wolinsky, et al. 2002. HIV preferentially infects HIV-specific CD4+ T cells. Nature 417:95-98.
24. Zhang, Z. Q., S. W. Wietgrefe, Q. Li, M. D. Shore, L. Duan, C. Reilly, J. D. Lifson, and A. T. Haase. 2004. 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.
25. Robertson, S. A. 2005. Seminal plasma and male factor signalling in the female reproductive tract. Cell Tissue Res. 322:43-52.
26. Robertson, S. A., L. R. Guerin, J. J. Bromfield, K. M. Branson, A. C. Ahlström, and A. S. Care. 2009. Seminal fluid drives expansion of the CD4+CD25+ T regulatory cell pool and induces tolerance to paternal alloantigens in mice. Biol. Reprod. 80:1036-1045.
27. Robertson, S. A., and D. J. Sharkey. 2001. The role of semen in induction of maternal immune tolerance to pregnancy. Semin. Immunol. 13:243-254.
28. Okamoto, M., R. Byrn, R. C. Eyre, T. Mullen, P. Church, and A. A. Kiessling. 2002. Seminal plasma induces programmed cell death in cultured peripheral blood mononuclear cells. AIDS Res. Hum. Retroviruses 18:797-803.
29. Bouvet, J. P., G. Grésenguet, and L. Bélec. 1997. Vaginal pH neutralization by semen as a cofactor of HIV transmission. Clin. Microbiol. Infect. 3:19-23.
30. Lai, S. K., K. Hida, S. Shukair, Y. Y. Wang, A. Figueiredo, R. Cone, T. J. Hope, and J. Hanes. 2009. Human immunodeficiency virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus. J. Virol. 83:11196-11200.
31. van't Wout, A. B., N. A. Kootstra, G. A. Mulder-Kampinga, N. Albrecht-van Lent, H. J. Scherpbier, J. Veenstra, K. Boer, R. A. Coutinho, F. Miedema, and H. Schuitemaker. 1994. Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission. J. Clin. Invest. 94:2060-2067.
32. Wolinsky, S. M., C. M. Wike, B. T. Korber, C. Hutto, W. P. Parks, L. L. Rosenblum K. J. Kunstman, M. R. Furtado, and J. L. Muñoz. 1992. Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants. Science 255:1134-1137.
33. Yamamoto, T., Y. Tsunetsugu-Yokota, Y. Y. Mitsuki, F. Mizukoshi, T. Tsuchiya, K. Terahara, Y. Inagaki, N. Yamamoto, K. Kobayashi, and J. Inoue. 2009. Selective transmission of R5 HIV-1 over X4 HIV-1 at the dendritic cell-T cell infectious synapse is determined by the T cell activation state. PLoS Pathog. 5: e1000279.
34. Zhu, T., H. Mo, N. Wang, D. S. Nam, Y. Cao, R. A. Koup, and D. D. Ho. 1993. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science 261:1179-1181.
35. Klatzmann, D., E. Champagne, S. Chamaret, J. Gruest, D. Guetard, T. Hercend, J. C. Gluckman, and L. Montagnier. 1984. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 312:767-768.
36. Dalgleish, A. G., P. C. Beverley, P. R. Clapham, D. H. Crawford, M. F. Greaves, and R. A. Weiss. 1984. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312:763-767.
37. Ji, C., E. Kopetzki, A. Jekle, K. G. Stubenrauch, X. Liu, J. Zhang, E. Rao, T. Schlothauer, S. Fischer, N. Cammack, et al. 2009. CD4-anchoring HIV-1 fusion inhibitor with enhanced potency and in vivo stability. J. Biol. Chem. 284:5175-5185.
38. Beaumier, C. M., L. D. Harris, S. Goldstein, N. R. Klatt, S. Whitted, J. McGinty, C. Apetrei, I. Pandrea, V. M. Hirsch, and J. M. Brenchley. 2009. CD4 downregulation by memory CD4+ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection. Nat. Med. 15:879-885.
39. Xiang, J., J. H. McLinden, R. A. Rydze, Q. Chang, T. M. Kaufman, D. Klinzman, and J. T. Stapleton. 2009. Viruses within the Flaviviridae decrease CD4 expression and inhibit HIV replication in human CD4+ cells. J. Immunol. 183:7860-7869.
40. Margolis, L., and R. Shattock. 2006. Selective transmission of CCR5-utilizing HIV-1: the 'gatekeeper' problem resolved? Nat. Rev. Microbiol. 4:312-317.
41. Keele, B. F., E. E. Giorgi, J. F. Salazar-Gonzalez, J. M. Decker, K. T. Pham, M. G. Salazar, C. Sun, T. Grayson, S. Wang, H. Li, et al. 2008. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc. Natl. Acad. Sci. USA 105:7552-7557.
42. Camara, M., T. N. Dieye, M. Seydi, A. A. Diallo, M. Fall, P. A. Diaw, P. S. Sow, S. Mboup, L. Kestens, and W. Jennes. 2010. Low-level CD4+ T cell activation in HIV-exposed seronegative subjects: influence of gender and condom use. J. Infect. Dis. 201:835-842.
43. Cohen, C. R., A. B. Moscicki, M. E. Scott, Y. Ma, S. Shiboski, E. Bukusi, I. Daud, A. Rebbapragada, J. Brown, and R. Kaul. 2010. Increased levels of immune activation in the genital tract of healthy young women from sub-Saharan Africa. AIDS 24:2069-2074.
44. Sattentau, Q. 2008. Avoiding the void: cell-to-cell spread of human viruses. Nat. Rev. Microbiol. 6:815-826.
45. Sourisseau, M., N. Sol-Foulon, F. Porrot, F. Blanchet, and O. Schwartz. 2007. Inefficient human immunodeficiency virus replication in mobile lymphocytes. J. Virol. 81:1000-1012.
46. Lehman, D. A., M. H. Chung, G. C. John-Stewart, B. A. Richardson, J. Kiarie, J. Kinuthia, and J. Overbaugh. 2008. HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent mother-to-child transmission. AIDS 22:1475-1485.
47. Sallé, B., P. Brochard, O. Bourry, A. Mannioui, T. Andrieu, S. Prevot, N. Dejucq-Rainsford, N. Dereuddre-Bosquet, and R. Le Grand. 2010. Infection of macaques after vaginal exposure to cell-associated simian immunodeficiency virus. J. Infect. Dis. 202:337-344.
48. Sato, H., J. Orenstein, D. Dimitrov, and M. Martin. 1992. Cell-to-cell spread of HIV-1 occurs within minutes and may not involve the participation of virus particles. Virology 186:712-724.
49. Vendrame, D., M. Sourisseau, V. Perrin, O. Schwartz, and F. Mammano. 2009. Partial inhibition of human immunodeficiency virus replication by type I interferons: impact of cell-to-cell viral transfer. J. Virol. 83:10527-10537.
50. Kim, K. A., M. Yolamanova, O. Zirafi, N. R. Roan, L. Staendker, W. G. Forssmann, A. Burgener, N. Dejucq-Rainsford, B. H. Hahn, G. M. Shaw, et al. 2010. Semenmediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI. Retrovirology 7:55.
51. Willott, G. M., and J. E. Allard. 1982. Spermatozoa-their persistence after sexual intercourse. Forensic Sci. Int. 19:135-154.
52. Lai, S. K., Y. Y. Wang, D. Wirtz, and J. Hanes. 2009. Micro-and macrorheology of mucus. Adv. Drug Deliv. Rev. 61:86-100.
53. Haimovici, F., K. H. Mayer, and D. J. Anderson. 1997. Quantitation of HIV-1-specific IgG, IgA, and IgM antibodies in human genital tract secretions. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 15:185-191.
54. Mselle, T. F., A. L. Howell, M. Ghosh, C. R. Wira, and C. L. Sentman. 2009. Human uterine natural killer cells but not blood natural killer cells inhibit human immunodeficiency virus type 1 infection by secretion of CXCL12. J. Virol. 83:11188-11195.
55. Ghosh, M., Z. Shen, J. V. Fahey, S. Cu-Uvin, K. Mayer, and C. R. Wira. 2010. Trappin-2/Elafin: a novel innate anti-human immunodeficiency virus-1 molecule of the human female reproductive tract. Immunology 129:207-219.
56. Hladik, F., and M. J. McElrath. 2008. Setting the stage: host invasion by HIV. Nat. Rev. Immunol. 8:447-457.
57. Zhu, J., F. Hladik, A. Woodward, A. Klock, T. Peng, C. Johnston, M. Remington, A. Magaret, D. M. Koelle, A. Wald, and L. Corey. 2009. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nat. Med. 15:886-892.
58. Norvell, M. K., G. I. Benrubi, and R. J. Thompson. 1984. Investigation of microtrauma after sexual intercourse. J. Reprod. Med. 29:269-271.
59. de Sousa, J. D., V. Müller, P. Lemey, and A. M. Vandamme. 2010. High GUD incidence in the early 20 century created a particularly permissive time window for the origin and initial spread of epidemic HIV strains. PLoS ONE 5: e9936.
60. Mauck, C. K., S. A. Ballagh, M. D. Creinin, D. H. Weiner, G. F. Doncel, R. N. Fichorova, J. L. Schwartz, N. Chandra, and M. M. Callahan. 2008. Six-day randomized safety trial of intravaginal lime juice. J. Acquir. Immune Defic. Syndr. 49:243-250.