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

  1. Author:
    Puri, A.
    Hug, P.
    Jernigan, K.
    Barchi, J.
    Kim, H. Y.
    Hamilton, J.
    Wiels, J.
    Murray, G. J.
    Brady, R. O.
    Blumenthal, R.

  2. Author Address

    Blumenthal R NCI, Sect Membrane Struct & Funct, Lab Expt & Computat Biol, Div Basic Sci,NIH Frederick, MD 21702 USA NCI, Sect Membrane Struct & Funct, Lab Expt & Computat Biol, Div Basic Sci,NIH Frederick, MD 21702 USA NINDS, Dev & Metab Neurol Branch, NIH Bethesda, MD 20892 USA NCI, Med Chem Lab, Div Basic Sci, NIH Bethesda, MD 20892 USA NIAAA, Lab Membrane Biochem & Biophys, NIH Rockville, MD 20852 USA Inst Gustave Roussy, CNRS UMR 1598 F-94805 Villejuif France
    1. Year: 1998
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 95
    2. 24
    3. Pages: 14435-14440
  4. Type of Article: Article
  1. 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-1(LAI) 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(alpha 1-->4)Gal(beta 1-->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. [References: 41]

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