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
. 1991 Oct 15;88(20):9297–9301. doi: 10.1073/pnas.88.20.9297

Human immunodeficiency virus can infect the apical and basolateral surfaces of human colonic epithelial cells.

J Fantini 1, N Yahi 1, J C Chermann 1
PMCID: PMC52701  PMID: 1718004

Abstract

The gastrointestinal tract is considered to be a major route of infection for the human immunodeficiency virus (HIV). To understand the interaction of HIV with epithelial cells of the intestinal mucosa, we have studied the infection of a human colon cancer cell clone HT-29-D4. The enterocyte-like differentiation of this clone can be modulated in vitro according to the concentration of glucose. We show that: (i) undifferentiated HT-29-D4 cells can be infected by HIV types 1 and 2 (HIV-1 and HIV-2) strains with no subsequent effect on cell growth; (ii) undifferentiated HT-29-D4 cells express a CD4-related antigen bearing epitopes of the immunoglobulin-like variable (V) region domains V1 and V2 of CD4 but lacking the epitope known to be involved in HIV envelope recognition; (iii) differentiated HT-29-D4 cells can be infected by HIV after an interaction with either the apical brush border membrane (luminal side) or the basolateral side (serosal side); (iv) the CD4-like molecule is restricted to the basolateral domain of differentiated cells; and (v) the infection is not inhibited by anti-CD4 monoclonal antibodies (mAbs) OKT4, OKT4A, Leu-3a, Bl4, 13-B-8-2, S-T4 or S-T40. We conclude that epithelial intestinal cells may represent a major site of entry for HIV. Infection of these epithelial cells may occur via the basolateral membrane by HIV-bearing lymphocytes or macrophages of the lamina propria and via the apical membrane by HIV present in the bowel lumen. This infection may remain silent for up to 9 months, and the virus can be rescued by cocultivation with lymphoid cells. These data may give an explanation for the long latent seronegative state that may occur in a HIV-infected individual.

Full text

PDF
9297

Images in this article

9298Image
on p.9298
9299Image
on p.9299
9299Image
on p.9299
9299Image
on p.9299

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. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  3. Basak S., Compans R. W. Polarized entry of canine parvovirus in an epithelial cell line. J Virol. 1989 Jul;63(7):3164–3167. doi: 10.1128/jvi.63.7.3164-3167.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clavel F., Guétard D., Brun-Vézinet F., Chamaret S., Rey M. A., Santos-Ferreira M. O., Laurent A. G., Dauguet C., Katlama C., Rouzioux C. Isolation of a new human retrovirus from West African patients with AIDS. Science. 1986 Jul 18;233(4761):343–346. doi: 10.1126/science.2425430. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Fantini J., Martin J. M., Luis J., Rémy L., Tirard A., Marvaldi J., Pichon J. Restricted localization of functional vasoactive intestinal peptide (VIP) receptors in in vitro differentiated human colonic adenocarcinoma cells (HT29-D4). Eur J Cell Biol. 1988 Aug;46(3):458–465. [PubMed] [Google Scholar]
  8. Fantini J., Rognoni J. B., Roccabianca M., Pommier G., Marvaldi J. Suramin inhibits cell growth and glycolytic activity and triggers differentiation of human colic adenocarcinoma cell clone HT29-D4. J Biol Chem. 1989 Jun 15;264(17):10282–10286. [PubMed] [Google Scholar]
  9. Fantini J., Verrier B., Marvaldi J., Mauchamp J. In vitro differentiated HT 29-D4 clonal cell line generates leakproof and electrically active monolayers when cultured in porous-bottom culture dishes. Biol Cell. 1989;65(2):163–169. [PubMed] [Google Scholar]
  10. Fuller S. D., von Bonsdorff C. H., Simons K. Cell surface influenza haemagglutinin can mediate infection by other animal viruses. EMBO J. 1985 Oct;4(10):2475–2485. doi: 10.1002/j.1460-2075.1985.tb03959.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fuller S., von Bonsdorff C. H., Simons K. Vesicular stomatitis virus infects and matures only through the basolateral surface of the polarized epithelial cell line, MDCK. Cell. 1984 Aug;38(1):65–77. doi: 10.1016/0092-8674(84)90527-0. [DOI] [PubMed] [Google Scholar]
  12. Galons J. P., Fantini J., Vion-Dury J., Cozzone P. J., Canioni P. Metabolic changes in undifferentiated and differentiated human colon adenocarcinoma cells studied by multinuclear magnetic resonance spectroscopy. Biochimie. 1989 Aug;71(8):949–961. doi: 10.1016/0300-9084(89)90077-1. [DOI] [PubMed] [Google Scholar]
  13. Gstraunthaler G. J. Epithelial cells in tissue culture. Ren Physiol Biochem. 1988 Jan-Feb;11(1-2):1–42. doi: 10.1159/000173147. [DOI] [PubMed] [Google Scholar]
  14. Landau N. R., Warton M., Littman D. R. The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4. Nature. 1988 Jul 14;334(6178):159–162. doi: 10.1038/334159a0. [DOI] [PubMed] [Google Scholar]
  15. Maddon P. J., Littman D. R., Godfrey M., Maddon D. E., Chess L., Axel R. The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell. 1985 Aug;42(1):93–104. doi: 10.1016/s0092-8674(85)80105-7. [DOI] [PubMed] [Google Scholar]
  16. Mathijs J. M., Hing M., Grierson J., Dwyer D. E., Goldschmidt C., Cooper D. A., Cunningham A. L. HIV infection of rectal mucosa. Lancet. 1988 May 14;1(8594):1111–1111. doi: 10.1016/s0140-6736(88)91932-0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. Owens R. J., Dubay J. W., Hunter E., Compans R. W. Human immunodeficiency virus envelope protein determines the site of virus release in polarized epithelial cells. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3987–3991. doi: 10.1073/pnas.88.9.3987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rabenandrasana C., Baghdiguian S., Marvaldi J., Fantini J. CD4 molecules are restricted to the basolateral membrane domain of in vitro differentiated human colon cancer cells (HT29-D4). FEBS Lett. 1990 Jun 4;265(1-2):75–79. doi: 10.1016/0014-5793(90)80887-o. [DOI] [PubMed] [Google Scholar]
  22. Rey F., Donker G., Hirsch I., Chermann J. C. Productive infection of CD4+ cells by selected HIV strains is not inhibited by anti-CD4 monoclonal antibodies. Virology. 1991 Mar;181(1):165–171. doi: 10.1016/0042-6822(91)90481-p. [DOI] [PubMed] [Google Scholar]
  23. Rey M. A., Spire B., Dormont D., Barre-Sinoussi F., Montagnier L., Chermann J. C. Characterization of the RNA dependent DNA polymerase of a new human T-lymphotropic retrovirus (lymphadenopathy associated virus). Biochem Biophys Res Commun. 1984 May 31;121(1):126–133. doi: 10.1016/0006-291x(84)90696-x. [DOI] [PubMed] [Google Scholar]
  24. Rodriguez D., Rodriguez J. R., Ojakian G. K., Esteban M. Vaccinia virus preferentially enters polarized epithelial cells through the basolateral surface. J Virol. 1991 Jan;65(1):494–498. doi: 10.1128/jvi.65.1.494-498.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Simons K., Fuller S. D. Cell surface polarity in epithelia. Annu Rev Cell Biol. 1985;1:243–288. doi: 10.1146/annurev.cb.01.110185.001331. [DOI] [PubMed] [Google Scholar]
  27. Willey R. L., Smith D. H., Lasky L. A., Theodore T. S., Earl P. L., Moss B., Capon D. J., Martin M. A. In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity. J Virol. 1988 Jan;62(1):139–147. doi: 10.1128/jvi.62.1.139-147.1988. [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