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Perspectives in Drug Discovery and Design

, Volume 5, Issue 1, pp 117–128 | Cite as

Sperm as mitogenic cofactors for HIV transmission

  • Virginia L. Scofield
Part IV. HIV Infection Of Spermatozoa

Summary

While studying interactions between gametes and somatic cells, we discovered that human sperm bind to HLA-DR via sperm surface structures that share antigenic epitopes with CD4. This finding has potential significance for HIV transmission, because: (i) HIV virions carry HLA-DR from infected cells; (ii) the HIV envelope glycoprotein gp160 has regions of homology with HLA-DR; and (iii) HLA-DR is a signal-transducing molecule of which the ligation triggers target-cell activation. If sperm bind to HIV by this recognition pathway, their selective binding to HLA-DR-expressing cells could deliver virus or viral antigens to muscosal cells of hematopoietic origin. For sperm not carrying virus, binding and cross-linking of HLA-DR on the same cells could trigger cell activation, thereby increasing target-cell susceptibility to HIV infection. We and others have shown that normal sperm bind to HIV in vitro, and that virus is present as nucleic acid in sperm from infected men. In the absence of virus, sperm from normal semen amplify cell activation by polyclonal mitogens or conventional antigen, and they dramatically increase the in vitro infectivity of free HIV particles. If similar events occur in the female reproductive tract after sexual contact, sperm-mediated target-cell activation may augment HIV transmission by this body fluid.

Keywords

Human Sperm Female Reproductive Tract Normal Sperm Glycoprotein Gp160 Normal Semen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Katz, D.R., Curr. Opin. Immunol., 1 (1988) 213.Google Scholar
  2. 2.
    Marrack, P., Winslow, G.M., Choi, Y., Scherer, M., Pullen, A., White, J. and Kappler, J.W., Immunol. Rev., 131 (1993) 79.Google Scholar
  3. 3.
    Ashida, E.R. and Scofield, V.L., Proc. Natl. Acad. Sci. USA, 84 (1987) 3395.Google Scholar
  4. 4.
    Scofield, V.L., Clisham, P.R., Bandyopadhyay, L., Gladstone, P., Zamboni, L. and Raghupathy, R., J. Immunol., 178 (1992) 1718.Google Scholar
  5. 5.
    Khoury, E.L. and Marshall, L.A., Cell Tissue Res., 262 (1990) 217.Google Scholar
  6. 6.
    Marx, J.L., Science, 245 (1989) 30.Google Scholar
  7. 7.
    Scofield, V.L., J. NIH Res., 4 (1992) 105 and 108–111.Google Scholar
  8. 8.
    Arthur, L.O., Bess Jr., J.W., Sowder II, R.C., Benveniste, R.E., Mann, D.L., Chermann, J.-C. and Henderson, L.E., Science, 258 (1992) 1935.Google Scholar
  9. 9.
    Golding, H., Robey, F.A., Gates III, F.T., Linder, W., Beining, P.R., Hoffman, T. and Golding, B., J. Exp. Med., 167 (1988) 914.Google Scholar
  10. 10.
    Lewis, D., Ulrich, R.G., Atassi, H. and Atassi, M.Z., Immunol. Lett., 24 (1990) 127.Google Scholar
  11. 11.
    Cordiali, P., Balzarotti, V., Morante, S., Parisi, V., Pugliese, O., Camponeschi, B. and Colizzi, V., Aids Res. Hum. Retroviruses, 3 (1992) 1561.Google Scholar
  12. 12.
    Habeshaw, J., Hounsell, E. and Dalgleish, A., Immunol. Today, 13 (1992) 207.Google Scholar
  13. 13.
    Fuleihan, R., Trede, N., Chatila, T. and Geta, R.S., Clin. Immunol. Immunopathol., 72 (1994) 357.Google Scholar
  14. 14.
    Goujard, C., Wallon, C., Rudent, A., Boue, F., Barre-Sinoussi, F. and Delfraissy, J.F., Aids, 8 (1994) 1397.Google Scholar
  15. 15.
    Hashimoto, K., Shigeta, S. and Baba, M., J. Aids, 10 (1995) 353.Google Scholar
  16. 16.
    Edwards, J.N.T. and Morris, H.B., Br. J. Obstet. Gynaecol., 92 (1985) 974.Google Scholar
  17. 17.
    Dussaix, E., Guetard, D., Gaudet, C., D'Almeida, M., Auer, J., Ellrodt, L., Montagnier, L. and Aroux, M., Res. Virol., 144 (1993) 487.Google Scholar
  18. 18.
    Nuovo, G.J., Becker, J., Simsir, A., Margiotta, M., Khalife, G. and Shevchuk, M., Am. J. Pathol., 144 (1994) 1142.Google Scholar
  19. 19.
    Baccetti, B., Benedetto, A., Burrini, A.G., Collodel, G., Ceccarini, E.C., Crisa, N., Caro, A., Estenoz, M., Garbuglia, A.R. and Massacesi, A., J. Cell Biol., 127 (1994) 903.Google Scholar
  20. 20.
    Bagasra, O., Farzadegan, H., Seshamma, T., Oakes, J.W., Saah, A. and Pomerantz, R.J., Aids, 8 (1994) 1669.Google Scholar
  21. 21.
    Scofield, V.L., Rao, B., Broder, S., Kennedy, C., Wallace, M., Graham, B. and Poiesz, B.J., Aids, 8 (1994) 1733.Google Scholar
  22. 22.
    Van Voorhis, B.J., Martinez, A., Mayer, K. and Anderson, D.J., Fertil. Steril., 55 (1991) 588.Google Scholar
  23. 23.
    Krieger, J.N., Coombs, R.W., Collier, A.C., Ross, S.O., Chaloupka, K., Cummings, D.K., Murphy, V.L. and Corey, L., J. Infect. Dis., 163 (1991) 386.Google Scholar
  24. 24.
    Mermin, J.H., Holodniy, M., Katzenstein, D.A. and Merigan, T.C., J. Infect. Dis., 174 (1991) 769.Google Scholar
  25. 25.
    Bendich, A., Borenfreund, E. and Sternberg, S.S., Science, 183 (1974) 857.Google Scholar
  26. 26.
    Zaneveld, L.J., De Jonge, C.J., Anderson, R.A. and Mack, S.R., Hum. Reprod., 6 (1991) 1265.Google Scholar
  27. 27.
    Parrish, J.J., Susko-Parrish, R., Handrow, R.R., Ax, R.L. and First, N.L., Gamete Res., 24 (1989) 403.Google Scholar
  28. 28.
    Krausz, C., Gervasi, G., Forti, G. and Baldi, E., Hum. Reprod., 9 (1994) 471.Google Scholar
  29. 29.
    Dohr, G.A., Motter, W., Leitinger, S., Desoye, G., Urdl, W., Winter, R., Wilders-Truschnig, M.M., Uchanska-Ziegler, B. and Ziegler, A., J. Immunol., 138 (1987) 3766.Google Scholar
  30. 30.
    Almeida, E.A.C., Huovila, A.-P.J., Sutherland, A.E., Stephens, L.E., Calarco, P.G., Shaw, L.M., Mercurio, A.M., Sonnenberg, A., Primakoff, P., Myles, D.G. and White, J.M., Cell, 81 (1995) 1095.Google Scholar
  31. 31.
    Mori, T., Wu, G.M. and Mori, E., Am. J. Reprod. Immunol., 26 (1991) 97.Google Scholar
  32. 32.
    Mori, T., Gou, M.W., Yoshida, H., Saito, S. and Mori, E., Biochem. Biophys. Res. Commun., 182 (1992) 527.Google Scholar
  33. 33.
    Guo, M.W., Watanabe, T., Mori, E. and Mori, T., Zygote, 3 (1995) 65.Google Scholar
  34. 34.
    Odum, N., Ledbetter, J.A., Martin, P., Geraghty, D., Tsu, T., Hansen, J.A. and Gladstone, P., Eur. J. Immunol., 21 (1991) 2121.Google Scholar
  35. 35.
    Odum, N., Martin, P.J., Schieven, G.L., Masewicz, Z., Hansen, J.A. and Ledbetter, J.A., Tissue Antigens, 38 (1991) 72.Google Scholar
  36. 36.
    Anderson, D.J., J. NIH Res., 4 (1992) 104 and 106–108.Google Scholar
  37. 37.
    Lingwood, C.A., Quinn, P.A., Wilansky, S., Nutikka, A., Ruhnke, H.L. and Miller, R.B., Biol. Reprod., 43 (1990) 694.Google Scholar
  38. 38.
    Ho, J.L., Attu, H.S., Geng, J., Basile, F.G., Almeida, M.G., Saito, A.Y., Laurence, J. and Johnson Jr., W.D., J. Exp. Med., 181 (1995) 1493.Google Scholar
  39. 39.
    Dobrescu, D., Ursea, B., Pope, M., Asch, A.S. and Posnett, D.N., Cell, 82 (1995) 753.Google Scholar
  40. 40.
    Wolff, H., Panhans, A., Stolz, W. and Meurer, M., Fertil. Steril., 60 (1993) 154.Google Scholar
  41. 41.
    Indraccolo, S., Gunzburg, W., Leif-Mosch, C., Erfle, V. and Salmons, B., Mamm. Genome, 6 (1995) 339.Google Scholar
  42. 42.
    Bavari, S. and Ulrich, R.G., Infect. Immun., 63 (1995) 427.Google Scholar
  43. 43.
    Torres, B.A., Griggs, N.G. and Johnson, H.M., Nature, 364 (1993) 152.Google Scholar
  44. 44.
    Lessley, B.A. and Garner, D.L., Gamete Res., 7 (1983) 49.Google Scholar
  45. 45.
    Pudney, J. and Anderson, D.J., Am. J. Pathol., 139 (1991) 149.Google Scholar
  46. 46.
    Poiesz, B.J., Ehrlich, G.D., Byrne, B.C., Wells, K., Kwok, S. and Sninsky, J., In De la Maza, L.M. and Peterson, E.M. (Eds.) Medical Virology, Vol. 9, Plenum, New York, NY, 1990, pp. 47–75.Google Scholar
  47. 47.
    Zhang, H., Zhang, Y., Spicer, T.P., Abbott, L.Z., Abbott, M. and Poiesz, B.J., Aids Res. Hum. Retroviruses, 9 (1993) 1287.Google Scholar
  48. 48.
    Raulston, J.E., Davis, C.H., Schmiel, D.H., Morgan, M.W. and Wyrick, P.B., J. Biol. Chem., 268 (1993) 23139.Google Scholar
  49. 49.
    Lingwood, C.A., Curr. Opin. Struct. Biol., 2 (1992) 693.Google Scholar
  50. 50.
    Nussbaum, O., Laster, J. and Loyter, A., Exp. Cell Res., 106 (1993) 11.Google Scholar
  51. 51.
    Fusi, F.M., Bronson, R.A., Hong, Y. and Ghebrehiwet, B., Mol. Reprod. Dev., 29 (1991) 180.Google Scholar
  52. 52.
    Thielens, N.M., Bally, I.M., Ebenbichler, C.F., Dierich, M.P. and Arlaud, G.J., J. Immunol., 151 (1993) 6583.Google Scholar
  53. 53.
    Curtis, B.M., Scharnowske, S. and Watson, A.J., Proc. Natl. Acad. Sci. USA, 89 (1992) 8356.Google Scholar
  54. 54.
    Fantini, J., Cook, D.G., Nathanson, N., Spitalnik, S.L. and Gonzalez-Scarano, F., Proc. Natl. Acad. Sci. USA, 90 (1993) 2700.Google Scholar
  55. 55.
    Moran, P.A., Diegel, M.L., Sais, J.C., Ledbetter, J.A. and Zarling, J.M., Aids Res. Hum. Retroviruses, 9 (1993) 455.Google Scholar
  56. 56.
    Butini, L., DeFougerolles, A.R., Vaccarezza, M., Graziosi, G., Cohen, D.I., Montroni, M., Springer, T.A., Pantaleo, G. and Fauci, A.S., Eur. J. Immunol., 24 (1994) 2191.Google Scholar
  57. 57.
    Diegel, M.L., Moran, P.A., Gilliland, L.K., Damle, N.K., Hayden, M.S., Zarling, J.M. and Ledbetter, J.A., Aids Res. Hum. Retroviruses, 9 (1993) 465.Google Scholar
  58. 58.
    Kinter, A.L., Poli, G., Maury, W., Folks, T.M. and Fauci, A.S., J. Virol., 64 (1990) 4306.Google Scholar
  59. 59.
    Oakes, J.W., Bagasra, O., Duan, L. and Pomerantz, R.J., Aids Res. Hum. Retroviruses, 10 (1994) 1213.Google Scholar
  60. 60.
    Kalter, D.C., Gendelman, H.E. and Meltzer, M.S., Immunol. Lett., 30 (1991) 219.Google Scholar
  61. 61.
    Busso, M., Thornwaite, J. and Resnick, J., Aids, 5 (1991) 1425.Google Scholar
  62. 62.
    Poli, G., Kinter, A., Jusement, J.A., Kehrl, J.H., Bressler, P., Stanley, S. and Fauci, A.S., Proc. Natl. Acad. Sci. USA, 87 (1990) 782.Google Scholar
  63. 63.
    Tang, S. and Levy, J.A., J. Virol. Methods, 33 (1991) 39.Google Scholar
  64. 64.
    Fais, S., Delle Fratte, F., Mancini, F., Cioni, V., Guadagno, M., Vetrano, G. and Pallone, F., J. Clin. Pathol., 44 (1991) 290.Google Scholar
  65. 65.
    Padian, N., Shibosky, S. and Jewell, N., J. Am. Med. Assoc., 266 (1991) 1664.Google Scholar
  66. 66.
    Miller, C.J., Curr. Top. Microbiol. Immunol., 188 (1994) 107.Google Scholar
  67. 67.
    Spira, A.I., Marx, P.A., Patterson, B.K., Mahoney, J., Koup, R.A., Wolinsky, S.M. and Ho, D.D., J. Exp. Med., 183 (1996) 215.Google Scholar
  68. 68.
    Kiessling, A.A., Crowell, R.C. and Connell, R.S., Proc. Natl. Acad. Sci. USA, 84 (1987) 8667.Google Scholar
  69. 69.
    Portis, J.L., McAtee, F.J. and Hayes, S.F., J. Virol., 178 (1987) 1037.Google Scholar
  70. 70.
    Doolittle, R.F., Feng, D.F., McClure, M.A. and Johnson, M.S., Curr. Top. Microbiol. Immunol., 61 (1990) 1.Google Scholar
  71. 71.
    Davidson, E.H. and Britten, R.J., Proc. Natl. Acad. Sci. USA, 88 (1991) 8401.Google Scholar
  72. 72.
    Niimi, N., Wajjwaku, W., Ando, Y., Ueda, N. and Yoshikai, Y., J. Virol., 69 (1995) 7269.Google Scholar
  73. 73.
    Miller, C., McGhee, J. and Gardner, M., Lab. Invest., 68 (1992) 129.Google Scholar
  74. 74.
    Held, W., Waanders, G.A., Shakhov, A.N., Scarpellino, L., Acha-Orbea, H. and McDonald, H.R., Cell, 74 (1993) 529.Google Scholar
  75. 75.
    Pucillo, C.E., Palmer, L.D. and Hodes, R.J., Immunol. Res., 14 (1995) 58.Google Scholar
  76. 76.
    Torres, B.A. and Johnson, H.M., Biochem. Biophys. Res. Commun., 200 (1994) 1059.Google Scholar

Copyright information

© ESCOM Science Publishers B.V 1996

Authors and Affiliations

  • Virginia L. Scofield
    • 1
  1. 1.Department of PediatricsHarbor-UCLA Medical CenterTorranceUSA

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