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(α1→4)Gal(β1→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.
Role of Glycosphingolipids in HIV-1 Entry: Requirement of Globotriosylceramide (Gb3) in CD4/CXCR4-dependent Fusion
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Anu Puri, Peter Hug, Kristine Jernigan, Patrick Rose, Robert Blumenthal; Role of Glycosphingolipids in HIV-1 Entry: Requirement of Globotriosylceramide (Gb3) in CD4/CXCR4-dependent Fusion. Biosci Rep 1 August 1999; 19 (4): 317–325. doi: https://doi.org/10.1023/A:1020554509642
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