The neutral glycosphingolipid globotriaosylceramide promotes fusion mediated by a CD4-dependent CXCR4-utilizing HIV type 1 envelope glycoprotein
- PMID: 9826718
- PMCID: PMC24391
- DOI: 10.1073/pnas.95.24.14435
The neutral glycosphingolipid globotriaosylceramide promotes fusion mediated by a CD4-dependent CXCR4-utilizing HIV type 1 envelope glycoprotein
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.
Figures
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References
-
- Maddon P J, Dalgleish A G, McDougal J S, Clapham P R, Weiss R A, Axel R. Cell. 1986;47:333–348. - PubMed
-
- Moore J P, Jameson B A, Weiss R A, Sattentau Q J. In: Viral Fusion Mechanisms. Bentz J, editor. Boca Raton, FL: CRC; 1993. pp. 233–289.
-
- Blumenthal R, Dimitrov D S. In: Handbook of Physiology. Hoffman J F, Jamieson J C, editors. New York: Oxford Univ. Press; 1997. pp. 563–603.
-
- Berger, E. A. (1997) AIDS 11, Suppl. A, S3–S16. - PubMed
-
- Broder C C, Dimitrov D S. Pathobiology. 1996;64:171–179. - PubMed
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