Skip to main content
NCBI home page
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
. 1993 Apr 1;90(7):2700–2704. doi: 10.1073/pnas.90.7.2700

Infection of colonic epithelial cell lines by type 1 human immunodeficiency virus is associated with cell surface expression of galactosylceramide, a potential alternative gp120 receptor.

J Fantini 1, D G Cook 1, N Nathanson 1, S L Spitalnik 1, F Gonzalez-Scarano 1
PMCID: PMC46163  PMID: 8464878

Abstract

The gastrointestinal tract plays a major role in the pathogenesis and pathophysiology of infection by the type 1 human immunodeficiency virus (HIV-1). It is a potential route for viral entry and it is the site of a number of complications, including both opportunistic infections and a primary HIV-induced enteropathy. Correspondingly, both in vivo and in vitro studies have demonstrated HIV infection of gastrointestinal cells of lymphoid and epithelial origin. HT-29, a human colonic epithelial cell line that is infectable with many HIV-1 strains, does not express CD4 protein or mRNA. Recent studies showed that antibodies recognizing a neutral glycolipid related to galactosylceramide (GalCer) in HT-29 cells inhibited HIV-1 infection of this cell line, extending previous findings in neural cells. In the current studies, we further analyzed the neutral glycolipids of HT-29 cells and showed that they contained authentic GalCer and that recombinant gp120 bound to this glycolipid. Moreover, by analyzing GalCer expression in clones derived from HT-29 and Caco-2 (another human colonic cell line), we observed that the level of expression of this glycolipid was associated with the sensitivity to HIV-1 infection. Subclones of Caco-2 did not express GalCer and were not infectable with any of three HIV-1 strains. These results strengthen the possibility that GalCer is an alternative receptor in CD4- cell lines. Furthermore, since GalCer is a major glycolipid in epithelial cells of the small intestine and colon, these results provide a structural basis for the binding of HIV-1 by gastrointestinal epithelial cells and the entry of the virus into those cells.

Full text

PDF
2700

Images in this article

2701Fig. 1
on p.2701
2702Fig. 2
on p.2702
2702Fig. 3
on p.2702
2703Fig. 4
on p.2703

Selected References

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

  1. Adachi A., Koenig S., Gendelman H. E., Daugherty D., Gattoni-Celli S., Fauci A. S., Martin M. A. Productive, persistent infection of human colorectal cell lines with human immunodeficiency virus. J Virol. 1987 Jan;61(1):209–213. doi: 10.1128/jvi.61.1.209-213.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnett S. W., Barboza A., Wilcox C. M., Forsmark C. E., Levy J. A. Characterization of human immunodeficiency virus type 1 strains recovered from the bowel of infected individuals. Virology. 1991 Jun;182(2):802–809. doi: 10.1016/0042-6822(91)90621-h. [DOI] [PubMed] [Google Scholar]
  3. Bartlett J. G., Belitsos P. C., Sears C. L. AIDS enteropathy. Clin Infect Dis. 1992 Oct;15(4):726–735. doi: 10.1093/clind/15.4.726. [DOI] [PubMed] [Google Scholar]
  4. Bhat S., Spitalnik S. L., Gonzalez-Scarano F., Silberberg D. H. Galactosyl ceramide or a derivative is an essential component of the neural receptor for human immunodeficiency virus type 1 envelope glycoprotein gp120. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7131–7134. doi: 10.1073/pnas.88.16.7131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Björk S., Breimer M. E., Hansson G. C., Karlsson K. A., Leffler H. Structures of blood group glycosphingolipids of human small intestine. A relation between the expression of fucolipids of epithelial cells and the ABO, Le and Se phenotype of the donor. J Biol Chem. 1987 May 15;262(14):6758–6765. [PubMed] [Google Scholar]
  6. Collman R., Balliet J. W., Gregory S. A., Friedman H., Kolson D. L., Nathanson N., Srinivasan A. An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1. J Virol. 1992 Dec;66(12):7517–7521. doi: 10.1128/jvi.66.12.7517-7521.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Collman R., Hassan N. F., Walker R., Godfrey B., Cutilli J., Hastings J. C., Friedman H., Douglas S. D., Nathanson N. Infection of monocyte-derived macrophages with human immunodeficiency virus type 1 (HIV-1). Monocyte-tropic and lymphocyte-tropic strains of HIV-1 show distinctive patterns of replication in a panel of cell types. J Exp Med. 1989 Oct 1;170(4):1149–1163. doi: 10.1084/jem.170.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ellrodt A., Barre-Sinoussi F., Le Bras P., Nugeyre M. T., Palazzo L., Rey F., Brun-Vezinet F., Rouzioux C., Segond P., Caquet R. Isolation of human T-lymphotropic retrovirus (LAV) from Zairian married couple, one with AIDS, one with prodromes. Lancet. 1984 Jun 23;1(8391):1383–1385. doi: 10.1016/s0140-6736(84)91877-4. [DOI] [PubMed] [Google Scholar]
  9. Fantini J., Abadie B., Tirard A., Remy L., Ripert J. P., el Battari A., Marvaldi J. Spontaneous and induced dome formation by two clonal cell populations derived from a human adenocarcinoma cell line, HT29. J Cell Sci. 1986 Jul;83:235–249. doi: 10.1242/jcs.83.1.235. [DOI] [PubMed] [Google Scholar]
  10. Fantini J., Yahi N., Baghdiguian S., Chermann J. C. Human colon epithelial cells productively infected with human immunodeficiency virus show impaired differentiation and altered secretion. J Virol. 1992 Jan;66(1):580–585. doi: 10.1128/jvi.66.1.580-585.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fantini J., Yahi N., Chermann J. C. Human immunodeficiency virus can infect the apical and basolateral surfaces of human colonic epithelial cells. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9297–9301. doi: 10.1073/pnas.88.20.9297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Harouse J. M., Bhat S., Spitalnik S. L., Laughlin M., Stefano K., Silberberg D. H., Gonzalez-Scarano F. Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide. Science. 1991 Jul 19;253(5017):320–323. doi: 10.1126/science.1857969. [DOI] [PubMed] [Google Scholar]
  13. Harouse J. M., Kunsch C., Hartle H. T., Laughlin M. A., Hoxie J. A., Wigdahl B., Gonzalez-Scarano F. CD4-independent infection of human neural cells by human immunodeficiency virus type 1. J Virol. 1989 Jun;63(6):2527–2533. doi: 10.1128/jvi.63.6.2527-2533.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heise C., Dandekar S., Kumar P., Duplantier R., Donovan R. M., Halsted C. H. Human immunodeficiency virus infection of enterocytes and mononuclear cells in human jejunal mucosa. Gastroenterology. 1991 Jun;100(6):1521–1527. doi: 10.1016/0016-5085(91)90648-5. [DOI] [PubMed] [Google Scholar]
  15. Holgersson J., Jovall P. A., Breimer M. E. Glycosphingolipids of human large intestine: detailed structural characterization with special reference to blood group compounds and bacterial receptor structures. J Biochem. 1991 Jul;110(1):120–131. doi: 10.1093/oxfordjournals.jbchem.a123530. [DOI] [PubMed] [Google Scholar]
  16. Karlsson K. A. Animal glycosphingolipids as membrane attachment sites for bacteria. Annu Rev Biochem. 1989;58:309–350. doi: 10.1146/annurev.bi.58.070189.001521. [DOI] [PubMed] [Google Scholar]
  17. Kotler D. P., Gaetz H. P., Lange M., Klein E. B., Holt P. R. Enteropathy associated with the acquired immunodeficiency syndrome. Ann Intern Med. 1984 Oct;101(4):421–428. doi: 10.7326/0003-4819-101-4-421. [DOI] [PubMed] [Google Scholar]
  18. Kotler D. P., Reka S., Borcich A., Cronin W. J. Detection, localization, and quantitation of HIV-associated antigens in intestinal biopsies from patients with HIV. Am J Pathol. 1991 Oct;139(4):823–830. [PMC free article] [PubMed] [Google Scholar]
  19. Ledeen R. W., Yu R. K. Gangliosides: structure, isolation, and analysis. Methods Enzymol. 1982;83:139–191. doi: 10.1016/0076-6879(82)83012-7. [DOI] [PubMed] [Google Scholar]
  20. Lehmann M., Rabenandrasana C., Rognoni J. B., Verrier B., Marvaldi J., Fantini J. Combination of culture on collagen gels and glucose starvation for cloning human colon cancer cells. Obtention of clones exhibiting different patterns of enterocytic differentiation. Cytotechnology. 1991 Feb;5(2):117–127. doi: 10.1007/BF00365428. [DOI] [PubMed] [Google Scholar]
  21. Lloyd K. O., Gordon C. M., Thampoe I. J., DiBenedetto C. Cell surface accessibility of individual gangliosides in malignant melanoma cells to antibodies is influenced by the total ganglioside composition of the cells. Cancer Res. 1992 Sep 15;52(18):4948–4953. [PubMed] [Google Scholar]
  22. Moyer M. P., Huot R. I., Ramirez A., Jr, Joe S., Meltzer M. S., Gendelman H. E. Infection of human gastrointestinal cells by HIV-1. AIDS Res Hum Retroviruses. 1990 Dec;6(12):1409–1415. doi: 10.1089/aid.1990.6.1409. [DOI] [PubMed] [Google Scholar]
  23. Nelson J. A., Wiley C. A., Reynolds-Kohler C., Reese C. E., Margaretten W., Levy J. A. Human immunodeficiency virus detected in bowel epithelium from patients with gastrointestinal symptoms. Lancet. 1988 Feb 6;1(8580):259–262. doi: 10.1016/s0140-6736(88)90348-0. [DOI] [PubMed] [Google Scholar]
  24. Omary M. B., Brenner D. A., de Grandpre L. Y., Roebuck K. A., Richman D. D., Kagnoff M. F. HIV-1 infection and expression in human colonic cells: infection and expression in CD4+ and CD4- cell lines. AIDS. 1991 Mar;5(3):275–281. doi: 10.1097/00002030-199103000-00005. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  27. Ranscht B., Clapshaw P. A., Price J., Noble M., Seifert W. Development of oligodendrocytes and Schwann cells studied with a monoclonal antibody against galactocerebroside. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2709–2713. doi: 10.1073/pnas.79.8.2709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sattentau Q. J., Arthos J., Deen K., Hanna N., Healey D., Beverley P. C., Sweet R., Truneh A. Structural analysis of the human immunodeficiency virus-binding domain of CD4. Epitope mapping with site-directed mutants and anti-idiotypes. J Exp Med. 1989 Oct 1;170(4):1319–1334. doi: 10.1084/jem.170.4.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tateno M., Gonzalez-Scarano F., Levy J. A. Human immunodeficiency virus can infect CD4-negative human fibroblastoid cells. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4287–4290. doi: 10.1073/pnas.86.11.4287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ullrich R., Heise W., Bergs C., L'age M., Riecken E. O., Zeitz M. Gastrointestinal symptoms in patients infected with human immunodeficiency virus: relevance of infective agents isolated from gastrointestinal tract. Gut. 1992 Aug;33(8):1080–1084. doi: 10.1136/gut.33.8.1080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ullrich R., Zeitz M., Heise W., L'age M., Höffken G., Riecken E. O. Small intestinal structure and function in patients infected with human immunodeficiency virus (HIV): evidence for HIV-induced enteropathy. Ann Intern Med. 1989 Jul 1;111(1):15–21. doi: 10.7326/0003-4819-111-1-15. [DOI] [PubMed] [Google Scholar]
  32. Yahi N., Baghdiguian S., Bolmont C., Fantini J. Replication and apical budding of HIV-1 in mucous-secreting colonic epithelial cells. J Acquir Immune Defic Syndr. 1992 Oct;5(10):993–1000. [PubMed] [Google Scholar]
  33. 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. 1992 Aug;66(8):4848–4854. doi: 10.1128/jvi.66.8.4848-4854.1992. [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