Role of Glycosphingolipids in HIV-1 Entry: Requirement of Globotriosylceramide (Gb3) in CD4/CXCR4-dependent Fusion |
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Authors: | Anu Puri Peter Hug Kristine Jernigan Patrick Rose Robert Blumenthal |
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Institution: | (1) Section of Membrane Structure and Function, LECB, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, P.O. Box B, Bldg. 469, Rm. 211, Miller Drive, Frederick, MD, 21702-1201, U.S.A |
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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( 1 4)Gal( 1 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. |
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Keywords: | HIV-1 entry/fusion glycosphingolipids |
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