The neutral glycosphingolipid globotriaosylceramide promotes fusion mediated by a CD4-dependent CXCR4-utilizing HIV type 1 envelope glycoprotein.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

The neutral glycosphingolipid globotriaosylceramide promotes fusion mediated by a CD4-dependent CXCR4-utilizing HIV type 1 envelope glycoprotein.

Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14435-40. Unique Identifier : AIDSLINE MED/99045702
Puri A; Hug P; Jernigan K; Barchi J; Kim HY; Hamilton J; Wiels J; Murray GJ; Brady RO; Blumenthal R; Section of Membrane Structure and Function, Laboratory of; Experimental and Computational Biology, Division of Basic; Sciences, National Cancer Institute, National Institutes of; Health, Frederick, MD 21702, USA.

Abstract: Previously, we showed that the addition of human erythrocyte glycosphingolipids (GSLs) to nonhuman CD4(+) or GSL-depleted human CD4(+) cells rendered those cells susceptible to HIV-1 envelope glycoprotein-mediated cell fusion. Individual components in the GSL mixture were isolated by fractionation on a silica-gel column and incorporated into the membranes of CD4(+) cells. GSL-supplemented target cells were then examined for their ability to fuse with TF228 cells expressing HIV-1LAI envelope glycoprotein. We found that one GSL fraction, fraction 3, exhibited the highest recovery of fusion after incorporation into CD4(+) nonhuman and GSL-depleted HeLa-CD4 cells and that fraction 3 contained a single GSL fraction. Fraction 3 was characterized by MS, NMR spectroscopy, enzymatic analysis, and immunostaining with an antiglobotriaosylceramide (Gb3) antibody and was found to be Gal(alpha1-->4)Gal(beta1-->4)Glc-Cer (Gb3). The addition of fraction 3 or Gb3 to GSL-depleted HeLa-CD4 cells recovered fusion, but the addition of galactosylceramide, glucosylceramide, the monosialoganglioside, GM3, lactosylceramide, globoside, the disialoganglioside, GD3, or alpha-galactosidase A-digested fraction 3 had no effect. Our findings show that the neutral GSL, Gb3, is required for CD4/CXCR4-dependent HIV-1 fusion.

Keywords: JOURNAL ARTICLE Acetylation Antigens, CD4/*PHYSIOLOGY Carbohydrate Conformation Carbohydrate Sequence Cell Fusion/DRUG EFFECTS/*PHYSIOLOGY Cell Line Erythrocytes/CHEMISTRY/PHYSIOLOGY Gene Products, env/DRUG EFFECTS/*PHYSIOLOGY Hela Cells Human HIV-1/DRUG EFFECTS/*PHYSIOLOGY Molecular Conformation Molecular Sequence Data Nuclear Magnetic Resonance, Biomolecular Receptors, CXCR4/DRUG EFFECTS/*PHYSIOLOGY Spectrum Analysis, Mass Support, U.S. Gov't, P.H.S. Trihexosylceramides/BLOOD/CHEMISTRY/*PHARMACOLOGY
990330
A9931029

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