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

Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2700-4. doi: 10.1073/pnas.90.7.2700.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma
  • Antibodies, Monoclonal
  • CD4 Antigens / analysis
  • Cell Membrane / metabolism*
  • Colonic Neoplasms
  • Epithelium / metabolism
  • Epithelium / microbiology
  • Fluorescent Antibody Technique
  • Galactosylceramides / analysis
  • Galactosylceramides / isolation & purification
  • Galactosylceramides / metabolism*
  • HIV Core Protein p24 / analysis
  • HIV Envelope Protein gp120 / metabolism*
  • HIV-1 / physiology*
  • Humans
  • Membrane Lipids / isolation & purification
  • Membrane Lipids / metabolism*
  • Protein Binding
  • Receptors, Virus / isolation & purification
  • Receptors, Virus / metabolism*
  • Tumor Cells, Cultured
  • Virus Replication*


  • Antibodies, Monoclonal
  • CD4 Antigens
  • Galactosylceramides
  • HIV Core Protein p24
  • HIV Envelope Protein gp120
  • Membrane Lipids
  • Receptors, Virus