Role of glycosphingolipids in HIV-1 entry: requirement of globotriosylceramide (Gb3) in CD4/CXCR4-dependent fusion. NLM AIDSLINE Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

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Role of glycosphingolipids in HIV-1 entry: requirement of globotriosylceramide (Gb3) in CD4/CXCR4-dependent fusion.

Biosci Rep. 1999 Aug;19(4):317-25. Unique Identifier : AIDSLINE MED/20055942
Puri A; Hug P; Jernigan K; Rose P; Blumenthal R; 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


Abstract: 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.


Keywords: JOURNAL ARTICLE Antigens, CD4/*METABOLISM Carbohydrate Sequence Cell Fusion Chromatography, Thin Layer CD4-Positive T-Lymphocytes/VIROLOGY Erythrocytes/VIROLOGY Glycosphingolipids/*METABOLISM Hela Cells Human HIV-1/*METABOLISM Models, Biological Molecular Sequence Data Receptors, CXCR4/*METABOLISM Support, U.S. Gov't, P.H.S. Trihexosylceramides/*METABOLISM Tumor Cells, Cultured Viral Fusion Proteins/*METABOLISM

KWDjournalarticleantigens,cd4/KWDmetabolismcarbohydratesequencecellfusionchromatography,thinlayercd4-positivet-lymphocytes/virologyerythrocytes/virologyglycosphingolipids/KWDmetabolismhelacellshumanhiv-1/KWDmetabolismmodels,biologicalmolecularsequencedatareceptors,cxcr4/KWDmetabolismsupport,uKWDsKWDgov't,pKWDhKWDsKWDtrihexosylceramides/KWDmetabolismtumorcells,culturedviralfusionproteins/KWDmetabolism
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