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Transcytosis of infectious human immunodeficiency virus across a tight human epithelial cell line barrier

Nature Medicinevolume 3pages4247 (1997) | Download Citation



Contact between various epithelial cell lines and HIV chronically infected mononuclear cell lines results in a massive and rapid budding of HIV virions toward the epithelium followed by their internalization into epithelial endosome-like structures. Here it is shown that as early as 30 min utes after apical contact, primary virus isolates generated from primary peripheral blood leukocytes from HIV-infected patients can cross an epithelial cell line barrier using transcytosis, the characteristic epithelial transcellular vesicular pathway. As the next step in the spread of infection, transcytosed HIV particles can productively infect mononuclear cells located at the basolateral side of the epithelial barrier. These observations suggest an alternative, rapid and efficient mechanism for transmission of HIV across an intact epithellial barrier.

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  1. 1

    Milman, G. & Sharma, O. Mechanisms of HIV/SIV mucosal transmission. AIDS Res. Hum. Retroviruses 10, 1305–1309 (1994).

  2. 2

    Fawcett, D.W. A Textbook of Histology (Chapman and Hall, New York, 1994).

  3. 3

    Simons, K. & Fuller, S.D. Cell surface polarity in epithelia. Annu. Rev. Cell Biol. 1, 243–288 (1985).

  4. 4

    Bomsel, M., Prydz, K., Parton, R.G., Gruenberg, J. & Simons, K. Endocytosis in filter-grown Madin-Darby canine kidney Cells. J. Cell Biol. 109, 3243–3258 (1989).

  5. 5

    Phillips, D.M. The role of Cell-to-Cell transmission in HIV infection. AIDS 8, 719–731 (1994).

  6. 6

    Fox, C.H., Kotler, D., Tiernay, A., Wilson, C.S. & Fauci, A.S. Detection of HIV–1 RNA in the lamina propria from patients with AIDS and gastrointestinal disease. J. Infect. Dis. 159, 467–471 (1989).

  7. 7

    Spira, A.I. et al. Cellular target of infection and route of viral dissemination after intravaginal inoculation of SIV into rhesus macaques. J. Exp. Med. 183, 215–225 (1996).

  8. 8

    Bourinbaiar, A.S. & Phillips, D.M. Transmission of human immunodeficiency virus from monocytes to epithelia. J. Acquir. Immune Defic. Syndr. 4, 56–63 (1991).

  9. 9

    Song, W., Bomsel, M., Casanova, J., Vaerman, J.-P. & Mostov, K. E. Stimulation of transcytosis of the polymeric immunoglobulin receptor by dimeric IgA. Proc. Natl. Acad. Sci. USA 91, 163–166 (1994).

  10. 10

    Yahi, N., Fantini, J., Baghdiguian, S. & Chermann, J.-C., Human T-lymphoblastoid Cells selected for growth in serum-free medium provide new tools for study of HIV replication and cytopathogenicity. J. Virol. Methods 34, 193–207 (1991).

  11. 11

    Folks, T.M. et al. Characterization of a promonocyte clone chronically infected with HIV and inducible by 13-phorbol-12-myristate acetate. J. Immunol. 140, 1117–1123 (1988).

  12. 12

    Bomsel, M. & Mostov, K.E. Sorting of plasma membrane proteins in epithelial Cells. Curr. Opin. Cell Biol. 3, 647–653 (1991).

  13. 13

    Weston, S.A. & Parish, C.R. Calcein: A novel marker for lymphocytes which enter lymph node. Cytometry 13, 739–749 (1992).

  14. 14

    Apodaca, G. et al. Characterization of Pseudomonas aeruginoso-induced MDCK Cell injury: Glycosylation defective host Cells are resistant to bacterial killing. Infect. Immun. 63, 1541–1551 (1995).

  15. 15

    Ball, J.M. et al. A polarized endometrial Cell line that binds and transports polymeric IgA. In Vitro Cell. Dev. Biol. 31, 196–206 (1995).

  16. 16

    Zweibaum, A., Laburthe, M., Grasset, E. & Louvard, D. Use of cultured Cell lines in studies of intestinal Cell differentiaaion and function. in The Handbookof Physiology, Sect. 6, The Gastrointestinal System, Vol. 4 (eds. Field, M. & Frizzel, R. A.) 223–255 (American Physiological Society, Bethesda, Maryland, 1991).

  17. 17

    Fais, S. et al. Unidirectional budding of HIV at the site of Cell-to-Cell contact is associated with co-polarization of interCellular adhesion molecules and HIV viral matrix protein. AIDS 9, 329–335 (1995).

  18. 18

    Yahi, N., Baghdiguian, S., Moreau, H. & Fantini, J. Galactosyl ceramide (or a closely related molecule) is the receptor for human immunodeficiency virus type 1 on human colon epithelial HT29 Cells. J. Virol. 66, 4848–4854 (1992).

  19. 19

    Harouse, J.M., Collman, R.G. & Gonzalez-Scarano, F. HIV-1 infection of SK-N-MC Cells: Domains of gp120 entry into a CD4-negative, galactosyl ceramide/3′ sulfo-galactosyl ceramide positive Cell line. J. Virol. 69, 7383–7390 (1995).

  20. 20

    Tschachler, E. et al. Epidermal Langerhans Cells, a target for HLTVM/LAV infection. J. Invest. Dermatol. 88, 233–237 (1987).

  21. 21

    van der Bijl, P., Lopes-Cardoza, M. & van Meer, G. Sorting of newly synthesized galactosphingolipids to the two surface domains of epithelial Cells. J. Cell Biol. 132, 813–821 (1996).

  22. 22

    Pearce-Pratt, R., Malamud, D. & Phillips, D.M. Role of the cytoskeleton in Cell-to-Cell transmission of human immunodeficiency virus. J. Virol. 68, 2898–2905 (1994).

  23. 23

    Shattock, R.J., Rizzardi, G.P., Hayes, P. & Griffin, G.E. Engagement of adhesion molecules (CD18, CD11a, CD45, CD44, and CD58) enhances human immunodeficiency virus type I replication in monocytic Cells through a tumor necrosis factor-modulated pathway. J. Infect. Dis. 174, 54–62 (1996).

  24. 24

    Amerongen, H.M. et al. Transepithelial transport of HIV-1 by intestinal M Cells: A mechanism for transmission of AIDS. J. Acquir. Immune Defic. Syndr. 4, 760–765 (1991).

  25. 25

    Carlos, T.M. & Harlan, J. M. Leukocyte endothelial adhesion molecules. Blood 84, 2068–2101 (1994).

  26. 26

    Bomsel, M. & Mostov, K.E. Possible role of both the α and βγ subunits of the het-erotrimeric G protein, Gs, in transcytosis of the polymeric immunoglobulin receptor. J. Biol. Chem. 268, 25824–25835 (1993).

  27. 27

    Dragic, T., Charneau, P., Clavel, F. & Alizon, M. Complementation of murine Cells for human immunodeficiency virus envelope CD4-mediated fusion in human murine heterokaryons. J. Virol. 66, 4794–4802 (1992).

  28. 28

    Russo-Marie, F., Roederer, M., Sager, B., Herzenberg, L.A. & Kaiser, D. Quantitation of β-galactosidase activity in single Cells of the bacterium Myxococcus xanthus. Proc. Natl. Acad. Sci. USA 90, 8194–8198 (1993).

  29. 29

    Nussbaum, O., Broder, C.C. & Berger, E.A. Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating Cell fusion-dependent reporter gene activation. J. Virol. 68, 5411–5422 (1994).

  30. 30

    Gilbert, T., LeBivic, A., Quaroni, A. & Rodriguez-Boulan, E. Microtubular organization and its involvement in the biogenetic pathway of plasma membrane proteins in CaCo-2 intestinal epithelial Cells. J. Cell Biol. 113, 275–288 (1991).

  31. 31

    Ranscht, B., Clapshaw, P.A., Price, J., Noble, M. & Seifert, W. Development of oligodendrocytes and Schwann Cells: Studies with a monoclonal antibody against galatocerebroside. Proc. Natl. Acad. Sci. USA 79, 2709–2713 (1982).

  32. 32

    DaCunha-Ferreira, R. et al. Changes in the rate of crypt epithelial Cell proliferation and mucosal morphology induced by a T-Cell-mediated response in human small intestine. Gastroenterology 98, 1255–1263 (1990).

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  1. U. 332, InstitutCochin de Génétique Moléculaire, 22, rue Méchain, F-75014, Paris, France

    • Morgane Bomsel


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