Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Feb 14;92(4):978–982. doi: 10.1073/pnas.92.4.978

Adherence of human immunodeficiency virus-infected lymphocytes to fetal placental cells: a model of maternal --> fetal transmission.

D H Schwartz 1, U K Sharma 1, E J Perlman 1, K Blakemore 1
PMCID: PMC42620  PMID: 7862677

Abstract

The precise timing and mechanism of in utero human immunodeficiency virus (HIV) infection are unknown, but transplacental transmission is likely. Term placentas from HIV+ pregnancies contain only rare HIV-infected cells whose origins and phenotypes remain controversial, and no correlation has been found between the presence of HIV in term placentas and transmission to offspring. Reports of trophoblast infectibility have not been reproducible and do not address the question of infection in the placental stroma, the cells in direct contact with fetal circulation. We report that primary cultures of fetal placental chorionic villus stromal cells, while not infectable in vitro, do support lethally irradiated HIV-infected peripheral blood mononuclear cells (PBMCs) in a form that permits rescue of HIV by activated PBMCs weeks later. Infected PBMCs adhere and become intimately associated with placental cells by a mechanism that is LFA-1 and CD4 independent but can be blocked by antibodies or soluble CD4 binding to cell surface-expressed HIV envelope. The ability to sustain infected irradiated cells was not shared by several trophoblast, fibroblast, or epithelial cell lines. This model has several features that are compatible with in utero transmission and allow testing of various agents proposed as interventions to block maternal-->fetal transmission. Placental stromal cells appear to inhibit apoptosis of HIV-infected, irradiated lymphocytes.

Full text

PDF
979

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amirhessami-Aghili N., Spector S. A. Human immunodeficiency virus type 1 infection of human placenta: potential route for fetal infection. J Virol. 1991 May;65(5):2231–2236. doi: 10.1128/jvi.65.5.2231-2236.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Apasov S., Redegeld F., Sitkovsky M. Cell-mediated cytotoxicity: contact and secreted factors. Curr Opin Immunol. 1993 Jun;5(3):404–410. doi: 10.1016/0952-7915(93)90060-6. [DOI] [PubMed] [Google Scholar]
  3. Backé E., Jiménez E., Unger M., Schäfer A., Jauniaux E., Vogel M. Demonstration of HIV-1 infected cells in human placenta by in situ hybridisation and immunostaining. J Clin Pathol. 1992 Oct;45(10):871–874. doi: 10.1136/jcp.45.10.871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chandwani S., Greco M. A., Mittal K., Antoine C., Krasinski K., Borkowsky W. Pathology and human immunodeficiency virus expression in placentas of seropositive women. J Infect Dis. 1991 May;163(5):1134–1138. doi: 10.1093/infdis/163.5.1134. [DOI] [PubMed] [Google Scholar]
  5. Courgnaud V., Lauré F., Brossard A., Bignozzi C., Goudeau A., Barin F., Bréchot C. Frequent and early in utero HIV-1 infection. AIDS Res Hum Retroviruses. 1991 Mar;7(3):337–341. doi: 10.1089/aid.1991.7.337. [DOI] [PubMed] [Google Scholar]
  6. Curtis B. M., Scharnowske S., Watson A. J. Sequence and expression of a membrane-associated C-type lectin that exhibits CD4-independent binding of human immunodeficiency virus envelope glycoprotein gp120. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8356–8360. doi: 10.1073/pnas.89.17.8356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Douglas G. C., Fry G. N., Thirkill T., Holmes E., Hakim H., Jennings M., King B. F. Cell-mediated infection of human placental trophoblast with HIV in vitro. AIDS Res Hum Retroviruses. 1991 Sep;7(9):735–740. doi: 10.1089/aid.1991.7.735. [DOI] [PubMed] [Google Scholar]
  8. Goldstein J., Braverman M., Salafia C., Buckley P. The phenotype of human placental macrophages and its variation with gestational age. Am J Pathol. 1988 Dec;133(3):648–659. [PMC free article] [PubMed] [Google Scholar]
  9. Helgason C. D., Shi L., Greenberg A. H., Shi Y., Bromley P., Cotter T. G., Green D. R., Bleackley R. C. DNA fragmentation induced by cytotoxic T lymphocytes can result in target cell death. Exp Cell Res. 1993 Jun;206(2):302–310. doi: 10.1006/excr.1993.1150. [DOI] [PubMed] [Google Scholar]
  10. Hildreth J. E., Orentas R. J. Involvement of a leukocyte adhesion receptor (LFA-1) in HIV-induced syncytium formation. Science. 1989 Jun 2;244(4908):1075–1078. doi: 10.1126/science.2543075. [DOI] [PubMed] [Google Scholar]
  11. Kesson A. M., Fear W. R., Kazazi F., Mathijs J. M., Chang J., King N. J., Cunningham A. L. Human immunodeficiency virus type 1 infection of human placental macrophages in vitro. J Infect Dis. 1993 Sep;168(3):571–579. doi: 10.1093/infdis/168.3.571. [DOI] [PubMed] [Google Scholar]
  12. Khong T. Y., Lane E. B., Robertson W. B. An immunocytochemical study of fetal cells at the maternal-placental interface using monoclonal antibodies to keratins, vimentin and desmin. Cell Tissue Res. 1986;246(1):189–195. doi: 10.1007/BF00219017. [DOI] [PubMed] [Google Scholar]
  13. Lairmore M. D., Cuthbert P. S., Utley L. L., Morgan C. J., Dezzutti C. S., Anderson C. L., Sedmak D. D. Cellular localization of CD4 in the human placenta. Implications for maternal-to-fetal transmission of HIV. J Immunol. 1993 Aug 1;151(3):1673–1681. [PubMed] [Google Scholar]
  14. Laurent-Crawford A. G., Krust B., Rivière Y., Desgranges C., Muller S., Kieny M. P., Dauguet C., Hovanessian A. G. Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells. AIDS Res Hum Retroviruses. 1993 Aug;9(8):761–773. doi: 10.1089/aid.1993.9.761. [DOI] [PubMed] [Google Scholar]
  15. Lewis S. H., Reynolds-Kohler C., Fox H. E., Nelson J. A. HIV-1 in trophoblastic and villous Hofbauer cells, and haematological precursors in eight-week fetuses. Lancet. 1990 Mar 10;335(8689):565–568. doi: 10.1016/0140-6736(90)90349-a. [DOI] [PubMed] [Google Scholar]
  16. Lowe S. W., Schmitt E. M., Smith S. W., Osborne B. A., Jacks T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature. 1993 Apr 29;362(6423):847–849. doi: 10.1038/362847a0. [DOI] [PubMed] [Google Scholar]
  17. Mano H., Chermann J. C. Fetal human immunodeficiency virus type 1 infection of different organs in the second trimester. AIDS Res Hum Retroviruses. 1991 Jan;7(1):83–88. doi: 10.1089/aid.1991.7.83. [DOI] [PubMed] [Google Scholar]
  18. Mattern C. F., Murray K., Jensen A., Farzadegan H., Pang J., Modlin J. F. Localization of human immunodeficiency virus core antigen in term human placentas. Pediatrics. 1992 Feb;89(2):207–209. [PubMed] [Google Scholar]
  19. Maury W., Potts B. J., Rabson A. B. HIV-1 infection of first-trimester and term human placental tissue: a possible mode of maternal-fetal transmission. J Infect Dis. 1989 Oct;160(4):583–588. doi: 10.1093/infdis/160.4.583. [DOI] [PubMed] [Google Scholar]
  20. McGann K. A., Collman R., Kolson D. L., Gonzalez-Scarano F., Coukos G., Coutifaris C., Strauss J. F., Nathanson N. Human immunodeficiency virus type 1 causes productive infection of macrophages in primary placental cell cultures. J Infect Dis. 1994 Apr;169(4):746–753. doi: 10.1093/infdis/169.4.746. [DOI] [PubMed] [Google Scholar]
  21. Miles S. A., Balden E., Magpantay L., Wei L., Leiblein A., Hofheinz D., Toedter G., Stiehm E. R., Bryson Y. Rapid serologic testing with immune-complex-dissociated HIV p24 antigen for early detection of HIV infection in neonates. Southern California Pediatric AIDS Consortium. N Engl J Med. 1993 Feb 4;328(5):297–302. doi: 10.1056/NEJM199302043280501. [DOI] [PubMed] [Google Scholar]
  22. Mues B., Langer D., Zwadlo G., Sorg C. Phenotypic characterization of macrophages in human term placenta. Immunology. 1989 Jul;67(3):303–307. [PMC free article] [PubMed] [Google Scholar]
  23. Nakamura Y., Ohta Y. Immunohistochemical study of human placental stromal cells. Hum Pathol. 1990 Sep;21(9):936–940. doi: 10.1016/0046-8177(90)90178-8. [DOI] [PubMed] [Google Scholar]
  24. Pearce-Pratt R., Phillips D. M. Studies of adhesion of lymphocytic cells: implications for sexual transmission of human immunodeficiency virus. Biol Reprod. 1993 Mar;48(3):431–445. doi: 10.1095/biolreprod48.3.431. [DOI] [PubMed] [Google Scholar]
  25. Peuchmaur M., Delfraissy J. F., Pons J. C., Emilie D., Vazeux R., Rouzioux C., Brossard Y., Papiernik E. HIV proteins absent from placentas of 75 HIV-1-positive women studied by immunohistochemistry. AIDS. 1991 Jun;5(6):741–745. doi: 10.1097/00002030-199106000-00015. [DOI] [PubMed] [Google Scholar]
  26. Phillips D. M., Bourinbaiar A. S. Mechanism of HIV spread from lymphocytes to epithelia. Virology. 1992 Jan;186(1):261–273. doi: 10.1016/0042-6822(92)90080-9. [DOI] [PubMed] [Google Scholar]
  27. Phillips D. M., Tan X. HIV-1 infection of the trophoblast cell line BeWo: a study of virus uptake. AIDS Res Hum Retroviruses. 1992 Sep;8(9):1683–1691. doi: 10.1089/aid.1992.8.1683. [DOI] [PubMed] [Google Scholar]
  28. Scott S., Pandolfi F., Kurnick J. T. Fibroblasts mediate T cell survival: a proposed mechanism for retention of primed T cells. J Exp Med. 1990 Dec 1;172(6):1873–1876. doi: 10.1084/jem.172.6.1873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Slusher J. T., Kuwahara S. K., Hamzeh F. M., Lewis L. D., Kornhauser D. M., Lietman P. S. Intracellular zidovudine (ZDV) and ZDV phosphates as measured by a validated combined high-pressure liquid chromatography-radioimmunoassay procedure. Antimicrob Agents Chemother. 1992 Nov;36(11):2473–2477. doi: 10.1128/aac.36.11.2473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Soeiro R., Rubinstein A., Rashbaum W. K., Lyman W. D. Maternofetal transmission of AIDS: frequency of human immunodeficiency virus type 1 nucleic acid sequences in human fetal DNA. J Infect Dis. 1992 Oct;166(4):699–703. doi: 10.1093/infdis/166.4.699. [DOI] [PubMed] [Google Scholar]
  31. Trapani J. A., Smyth M. J. Killing by cytotoxic T cells and natural killer cells: multiple granule serine proteases as initiators of DNA fragmentation. Immunol Cell Biol. 1993 Jun;71(Pt 3):201–208. doi: 10.1038/icb.1993.22. [DOI] [PubMed] [Google Scholar]
  32. Weeks B. S., Klotman M. E., Holloway E., Stetler-Stevenson W. G., Kleinman H. K., Klotman P. E. HIV-1 infection stimulates T cell invasiveness and synthesis of the 92-kDa type IV collagenase. AIDS Res Hum Retroviruses. 1993 Jun;9(6):513–518. doi: 10.1089/aid.1993.9.513. [DOI] [PubMed] [Google Scholar]
  33. Yagel S., Livni N., Zacut D., Gallily R. Characterization and localization of human placental mononuclear phagocytes by monoclonal antibodies and other cell markers. Isr J Med Sci. 1990 May;26(5):243–249. [PubMed] [Google Scholar]
  34. Yu M. T., Yu C. Y., Yu C. X., Maidman J., Warburton D. Improved methods of direct and cultured chromosome preparations from chorionic villous samples. Am J Hum Genet. 1986 Apr;38(4):576–581. [PMC free article] [PubMed] [Google Scholar]
  35. Zachar V., Spire B., Hirsch I., Chermann J. C., Ebbesen P. Human transformed trophoblast-derived cells lacking CD4 receptor exhibit restricted permissiveness for human immunodeficiency virus type 1. J Virol. 1991 Apr;65(4):2102–2107. doi: 10.1128/jvi.65.4.2102-2107.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES