Binding of human immunodeficiency virus type I (HIV-1) gp120 to galactosylceramide (GalCer): relationship to the V3 loop.
The primary receptor for the human immunodeficiency virus (HIV) is the CD4 molecule. However, a large body of evidence has demonstrated that some cells that do not express the CD4 receptor can be infected by HIV-1 and HIV-2, indicating that an alternative mechanism of infection must exist for some cell types. Recently it was reported that antibodies against the glycosphingolipid, galactosylceramide (Gal beta 1-1'Cer;GalCer), blocked infection of several CD4 negative cell lines derived from the brain and colon. The hypothesis that GalCer might be involved in the process of HIV entry into these cells was further supported by the finding that recombinant gp120 bound GalCer with high affinity in a high performance thin layer chromatography (HPTLC) binding assay. We have examined the interactions between GalCer and gp120, and found that the oligosaccharides that constitute a large proportion of the molecular mass of this glycoprotein are not involved in binding to this glycolipid. Furthermore, using a panel of monoclonal and monospecific antibodies we have determined that gp120 binds GalCer, and the related molecule 3' sulfo galactosylceramide (sulfatide), at a site that is conformationally close to the its principal neutralizing domain (V3 loop) or at the V3 loop itself.
Cook
D G
DG
Department of Neurology, University of Pennsylvania Medical Center, Philadelphia 19104-6146.
Fantini
J
J
Spitalnik
S L
SL
Gonzalez-Scarano
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005699:Galactosylceramides / Q000378:metabolism*; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D005699:Galactosylceramides; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments