Role of glycosphingolipids in HIV-1 entry: requirement of globotriosylceramide (Gb3) in CD4/CXCR4-dependent fusion.
We have recently shown that addition of human erythrocyte glycosphingolipids (GSL) to non-human CD4+ or GSL-depleted human CD4+ cells rendered those cells susceptible to gp120-gp41-mediated cell fusion (Puri et al., BBRC, 1998). One GSL fraction (Fraction 3) isolated from human erythrocyte GSL mixture exhibited the highest recovery of fusion following incorporation into CD4+ non-human and GSL-depleted HeLa-CD4 cells (HeLa-CD4/GSL-). Structural analysis of Fraction 3 showed that this GSL had identical head group as the known GSL, Gal(alpha1-->4)Gal(beta1-->4)Glc-Ceramide (Gb3) (Puri et al., PNAS, 1998). Here we report that presence of Gb3 in CD4+/CXCR4+ cells but not CD4+/CXCR4 cells allows fusion with HIV-1Lai-envelope glycoprotein expressing cells (TF228). Therefore, Gb3 functions in conjunction with HIV-1 co-receptor, CXCR4 to promote fusion. We propose that Gb3 functions by recruiting CD4 and/or CXCR4 at the fusion site through structurally specific interactions.
Puri
A
A
Section of Membrane Structure and Function, LECB, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA. apuri@helix.nih.gov
Hug
P
P
Jernigan
K
K
Rose
P
P
Blumenthal
R
R
D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002240:Carbohydrate Sequence; D002459:Cell Fusion; D002855:Chromatography, Thin Layer; D004912:Erythrocytes / Q000821:virology; D006028:Glycosphingolipids / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014281:Trihexosylceramides / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014760:Viral Fusion Proteins / Q000378:metabolism*
D015704:CD4 Antigens; D006028:Glycosphingolipids; D019718:Receptors, CXCR4; D014281:Trihexosylceramides; D014760:Viral Fusion Proteins; C018549:globotriaosylceramide