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.
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Moyer, M.P., Huot, R.I., Ramirez, A., Joe, S., Meltzer, M.S. and Gendelman, H.E., Aids Res. Hum. Retroviruses, 6 (1990) 1409.
Adachi, A., Koenig, S., Gendelman, H.E., Daugherty, D., Gatoni-Celli, S., Fauci, A.S. and Martin, M.A., J. Virol., 61 (1987) 209.
Omary, M.B., Brenner, D.A., de Grandpre, L.Y., Roebuck, K.A., Richman, D.D. and Kagnoff, M.F., Aids, 5 (1991) 275.
Barnett, S.W., Barboza, A., Wilcox, C.M., Forsmark, C.E. and Levi, J.A., Virology, 182 (1991) 802.
Yahi, N., Baghdiguian, S., Moreau, H. and Fantini, J., J. Virol., 66 (1992) 4848.
Fantini, J., Cook, D.G., Nathanson, N., Spitalnik, S.L. and Gonzalez-Scarano, F., Proc. Natl. Acad. Sci. USA, 90 (1993) 2700.
Harouse, J.M., Bhat, S., Spitalnik, S.L., Laughlin, M., Stefano, K., Silberberg, D.H. and Gonzalez-Scarano, F., Science, 253 (1991) 320.
Bhat, S., Spitalnik, S.L., Gonzalez-Scarano, F. and Silberberg, D.H., Proc. Natl. Acad. Sci. USA, 88 (1991) 7131.
Long, D., Berson, J.F., Cook, D.G. and Doms, R.W., J. Virol., 68 (1994) 5890.
Bjork, S., Breimer, M.E., Haunson, G.C. and Leffler, H., J. Biol. Chem., 262 (1987) 6758.
Holgerson, J., Jovall, P.A. and Breimer, M.E., J. Biochem., 110 (1991) 120.
Yahi, N., Spitalnik, S.L., Stefano, K.A., De Micco, P., Gonzalez-Scarano, F. and Fantini, J., Virology, 204 (1994) 550.
Kotler, D.P., Gaetz, H.P., Lange, M., Klein, E.B. and Holt, P.R., Ann. Intern. Med., 101 (1984) 421.
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.
Kostianovsky, M. and Grimley, P.M., Ultrastruct. Pathol., 8 (1985) 123.
Onerheim, R.M., Wang, N.-S., Gilmore, N. and Jothy, S., Am. J. Clin. Pathol., 82 (1984) 280.
Yoffe, B., Petrie, B.L., Noonan, C.A. and Hollinger, F.B., Lab. Invest., 61 (1989) 303.
Shapiro, S.H. and Klavins, J.V., Ultrastruct. Pathol., 17 (1993) 557.
Pinto, M., Appay, M.D. and Simon-Assman, P., Biol. Cell, 44 (1982) 193.
Phillips, D.M. and Bourinbaiar, A.S., Virology, 186 (1992) 261.
Fantini, J., Yahi, N., Baghdiguian, S. and Chermann, J.C., J. Virol., 66 (1992) 580.
Fantini, J., Verrier, B., Marvaldi, J. and Mauchamp, J., Biol. Cell, 65 (1989) 163.
Fantini, J., Yahi, N. and Chermann, J.C., Proc. Natl. Acad. Sci. USA, 88 (1991) 9297.
Cutz, E., Rhoads, J.M., Drumm, B., Sherman, P.M., Duvie, P.R. and Forstner, G.G., New Engl. J. Med., 230 (1989) 646.
Yahi, N., Baghdiguian, S., Bolmont, C. and Fantini, J., J. Aids, 5 (1992) 993.
Ullrich, R., Zeitz, M., Heise, W., Lage, M., Höffken, G. and Riecken, E.O., Ann. Intern. Med., 111 (1989) 15.
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.
Bourinbaiar, A.S. and Phillips, D.M., J. Aids, 4 (1991) 56.
Ghadially, F.M., Ultrastructural Pathology of the Cell and Matrix, 3rd ed., Butter-Worths, London, 1988.
Shapiro, S.H., Wesseley, Z. and Lipper, S., Ultrastruct. Pathol., 8 (1985) 241.
Kawaguchi, M., Ikegiri, N., Miyakoda, V., Eguchi, N., Abe, H. and Tanikawa, K., J. Clin. Electron. Microsc., 8 (1975) 362.
Tandler, B., Erlandson, R.A., Smith, A.L. and Wynder, E.L., J. Cell Biol., 41 (1969) 477.
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.
Dobbins, W.O. and Weinstein, W.M., Gastroenterology, 88 (1985) 738.
Mathan, E.M., Griffin, G.E. and Batman, P., J. Pathol., 161 (1990) 114.
Benhamou, Y., Hilmarsdottir, I., Desporte-Livage, I., Hoang, C., Datry, A., Danis, M., Gentilini, M. and Opolon, P., Dig. Dis. Sci., 39 (1994) 2163.
Patterson, B.K., Ehrenpreis, E.D. and Yokoo, H., Am. J. Clin. Pathol., 99 (1993) 24.
Smith, P.D. and Mai, V.E.H., Gastroenterol. Clin. North Am., 21 (1992) 331.
Dayanithi, G., Yahi, N., Baghdiguian, S. and Fantini, J., Cell Calcium, 18 (1995) 9.
Dyer, C.A. and Benjamins, J.A., J. Neurosci. Res., 30 (1991) 699.
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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
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DOI: https://doi.org/10.1007/BF02174003