Morphological alterations associated with HIV infection of CD4/GalCer+ human intestinal epithelial cells

Summary

The ultrastructural alterations induced by human immunodeficiency virus type 1 (HIV-1) in the human colon epithelial cell line HT-29 infected in vitro have been evaluated. These cells express high levels of galactosyl ceramide (GalCer), an alternative receptor for HIV-1 surface envelope glycoprotein gp120. Using immunolabelling for electron microscopy and immunofluorescence techniques, we detected the GalCer receptor in both the apical and basolateral membranes of differentiated HT-29 subclones. This nonpolar distribution is consistent with our previous observation that HIV infects both the apical and basolateral surfaces of epithelial cells in vitro. A transmission electron microscopy study demonstrated two major ultrastructural perturbations in the HIV-producing cells: (i) an unusual number of secretory granules; and (ii) the appearance of intracellular lumina with disorganized microvilli, indicating a defect in striated border assembly and differentiation. In addition to these morphological alterations, our study revealed the presence of fat vacuoles, concentric membranous bodies, tubuloreticular inclusions and giant mitochondria in the cytoplasm of HIV-infected cells. Taken together, these abnormalities could account for HIV-induced enteropathy, consisting of chronic diarrhea and malabsorption in the absence of enteric pathogens.

This is a preview of subscription content, access via your institution.

References

  1. 1

    Moyer, M.P., Huot, R.I., Ramirez, A., Joe, S., Meltzer, M.S. and Gendelman, H.E., Aids Res. Hum. Retroviruses, 6 (1990) 1409.

    Google Scholar 

  2. 2

    Adachi, A., Koenig, S., Gendelman, H.E., Daugherty, D., Gatoni-Celli, S., Fauci, A.S. and Martin, M.A., J. Virol., 61 (1987) 209.

    Google Scholar 

  3. 3

    Omary, M.B., Brenner, D.A., de Grandpre, L.Y., Roebuck, K.A., Richman, D.D. and Kagnoff, M.F., Aids, 5 (1991) 275.

    Google Scholar 

  4. 4

    Barnett, S.W., Barboza, A., Wilcox, C.M., Forsmark, C.E. and Levi, J.A., Virology, 182 (1991) 802.

    Google Scholar 

  5. 5

    Yahi, N., Baghdiguian, S., Moreau, H. and Fantini, J., J. Virol., 66 (1992) 4848.

    Google Scholar 

  6. 6

    Fantini, J., Cook, D.G., Nathanson, N., Spitalnik, S.L. and Gonzalez-Scarano, F., Proc. Natl. Acad. Sci. USA, 90 (1993) 2700.

    Google Scholar 

  7. 7

    Harouse, J.M., Bhat, S., Spitalnik, S.L., Laughlin, M., Stefano, K., Silberberg, D.H. and Gonzalez-Scarano, F., Science, 253 (1991) 320.

    Google Scholar 

  8. 8

    Bhat, S., Spitalnik, S.L., Gonzalez-Scarano, F. and Silberberg, D.H., Proc. Natl. Acad. Sci. USA, 88 (1991) 7131.

    Google Scholar 

  9. 9

    Long, D., Berson, J.F., Cook, D.G. and Doms, R.W., J. Virol., 68 (1994) 5890.

    Google Scholar 

  10. 10

    Bjork, S., Breimer, M.E., Haunson, G.C. and Leffler, H., J. Biol. Chem., 262 (1987) 6758.

    Google Scholar 

  11. 11

    Holgerson, J., Jovall, P.A. and Breimer, M.E., J. Biochem., 110 (1991) 120.

    Google Scholar 

  12. 12

    Yahi, N., Spitalnik, S.L., Stefano, K.A., De Micco, P., Gonzalez-Scarano, F. and Fantini, J., Virology, 204 (1994) 550.

    Google Scholar 

  13. 13

    Kotler, D.P., Gaetz, H.P., Lange, M., Klein, E.B. and Holt, P.R., Ann. Intern. Med., 101 (1984) 421.

    Google Scholar 

  14. 14

    Grimley, P.M., Kang, Y.H., Frederick, W., Rook, A.H., Kostianovsky, M., Sonnabend, J.A., Macher, A.M., Quinnan, G.V., Friedman, R.M. and Masur, H., Am. J. Clin. Pathol., 8 (1984) 147.

    Google Scholar 

  15. 15

    Kostianovsky, M. and Grimley, P.M., Ultrastruct. Pathol., 8 (1985) 123.

    Google Scholar 

  16. 16

    Onerheim, R.M., Wang, N.-S., Gilmore, N. and Jothy, S., Am. J. Clin. Pathol., 82 (1984) 280.

    Google Scholar 

  17. 17

    Yoffe, B., Petrie, B.L., Noonan, C.A. and Hollinger, F.B., Lab. Invest., 61 (1989) 303.

    Google Scholar 

  18. 18

    Shapiro, S.H. and Klavins, J.V., Ultrastruct. Pathol., 17 (1993) 557.

    Google Scholar 

  19. 19

    Pinto, M., Appay, M.D. and Simon-Assman, P., Biol. Cell, 44 (1982) 193.

    Google Scholar 

  20. 20

    Phillips, D.M. and Bourinbaiar, A.S., Virology, 186 (1992) 261.

    Google Scholar 

  21. 21

    Fantini, J., Yahi, N., Baghdiguian, S. and Chermann, J.C., J. Virol., 66 (1992) 580.

    Google Scholar 

  22. 22

    Fantini, J., Verrier, B., Marvaldi, J. and Mauchamp, J., Biol. Cell, 65 (1989) 163.

    Google Scholar 

  23. 23

    Fantini, J., Yahi, N. and Chermann, J.C., Proc. Natl. Acad. Sci. USA, 88 (1991) 9297.

    Google Scholar 

  24. 24

    Cutz, E., Rhoads, J.M., Drumm, B., Sherman, P.M., Duvie, P.R. and Forstner, G.G., New Engl. J. Med., 230 (1989) 646.

    Google Scholar 

  25. 25

    Yahi, N., Baghdiguian, S., Bolmont, C. and Fantini, J., J. Aids, 5 (1992) 993.

    Google Scholar 

  26. 26

    Ullrich, R., Zeitz, M., Heise, W., Lage, M., Höffken, G. and Riecken, E.O., Ann. Intern. Med., 111 (1989) 15.

    Google Scholar 

  27. 27

    Takiya, C.M., Elia, C., Madi, K., Zaltman, C., Trajman, A., Belo, M.T. and Chazas, V., VIIth International Conference on AIDS, Florence, Italy, 16–21 June 1991, Abstract M.B. 2283.

  28. 28

    Bourinbaiar, A.S. and Phillips, D.M., J. Aids, 4 (1991) 56.

    Google Scholar 

  29. 29

    Ghadially, F.M., Ultrastructural Pathology of the Cell and Matrix, 3rd ed., Butter-Worths, London, 1988.

    Google Scholar 

  30. 30

    Shapiro, S.H., Wesseley, Z. and Lipper, S., Ultrastruct. Pathol., 8 (1985) 241.

    Google Scholar 

  31. 31

    Kawaguchi, M., Ikegiri, N., Miyakoda, V., Eguchi, N., Abe, H. and Tanikawa, K., J. Clin. Electron. Microsc., 8 (1975) 362.

    Google Scholar 

  32. 32

    Tandler, B., Erlandson, R.A., Smith, A.L. and Wynder, E.L., J. Cell Biol., 41 (1969) 477.

    Google Scholar 

  33. 33

    Somasundaran, M., Zapp, M.L., Beattie, L.K., Pang, L., Byron, K.S., Bassell, G.J., Sullivan, J.L. and Singer, R.H., J. Cell Biol., 126 (1994) 1353.

    Google Scholar 

  34. 34

    Dobbins, W.O. and Weinstein, W.M., Gastroenterology, 88 (1985) 738.

    Google Scholar 

  35. 35

    Mathan, E.M., Griffin, G.E. and Batman, P., J. Pathol., 161 (1990) 114.

    Google Scholar 

  36. 36

    Benhamou, Y., Hilmarsdottir, I., Desporte-Livage, I., Hoang, C., Datry, A., Danis, M., Gentilini, M. and Opolon, P., Dig. Dis. Sci., 39 (1994) 2163.

    Google Scholar 

  37. 37

    Patterson, B.K., Ehrenpreis, E.D. and Yokoo, H., Am. J. Clin. Pathol., 99 (1993) 24.

    Google Scholar 

  38. 38

    Smith, P.D. and Mai, V.E.H., Gastroenterol. Clin. North Am., 21 (1992) 331.

    Google Scholar 

  39. 39

    Dayanithi, G., Yahi, N., Baghdiguian, S. and Fantini, J., Cell Calcium, 18 (1995) 9.

    Google Scholar 

  40. 40

    Dyer, C.A. and Benjamins, J.A., J. Neurosci. Res., 30 (1991) 699.

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Stephen Baghdiguian.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Baghdiguian, S., Yahi, N. & Fantini, J. Morphological alterations associated with HIV infection of CD4/GalCer+ human intestinal epithelial cells. Perspectives in Drug Discovery and Design 5, 73–82 (1996). https://doi.org/10.1007/BF02174003

Download citation

Keywords

  • Ceramide
  • Galactosyl
  • Human Intestinal Epithelial Cell
  • Human Colon Epithelial Cell
  • Giant Mitochondrion