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.
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.
Fantini
J
J
Department of Neurology, University of Pennsylvania Medical Center, Philadelphia 19104-6146.
Cook
D G
DG
Nathanson
N
N
Spitalnik
S L
SL
Gonzalez-Scarano
F
F
D000230:Adenocarcinoma; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000032:analysis; D002462:Cell Membrane / Q000378:metabolism*; D003110:Colonic Neoplasms; D004848:Epithelium / Q000378:metabolism / Q000382:microbiology; D005455:Fluorescent Antibody Technique; D005699:Galactosylceramides / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D016655:HIV Core Protein p24 / Q000032:analysis; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008563:Membrane Lipids / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D011991:Receptors, Virus / Q000302:isolation & purification / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D005699:Galactosylceramides; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D008563:Membrane Lipids; D011991:Receptors, Virus