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Medientyp:
E-Artikel
Titel:
The Neutral Glycosphingolipid Globotriaosylceramide Promotes Fusion Mediated by a CD4-Dependent CXCR4-Utilizing HIV Type 1 Envelope Glycoprotein
Beteiligte:
Puri, Anu;
Hug, Peter;
Jernigan, Kristine;
Barchi, Joseph;
Kim, Hee-Yong;
Hamilton, Jillon;
Wiels, Joelle;
Murray, Gary J.;
Brady, Roscoe O.;
Blumenthal, Robert
Erschienen:
National Academy of Sciences of the United States of America, 1998
Erschienen in:
Proceedings of the National Academy of Sciences of the United States of America, 95 (1998) 24, Seite 14435-14440
Sprache:
Englisch
ISSN:
0027-8424
Entstehung:
Anmerkungen:
Beschreibung:
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-1LAIenvelope 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(α 1→ 4)Gal(β 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 α -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.