Glycans and Proteoglycans Are Involved in the Interactions of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein and of SDF-1α with Membrane Ligands of CD4+ CXCR4+ Cells

• Published in: Virology (New York, N.Y.) N.Y.), 1999-12, Vol.265 (2), p.354-364
• Main Authors: Mbemba, Elisabeth, Benjouad, A., Saffar, L., Gattegno, L.
• Format: Article
• Language: English
• Subjects: CD4 antigen; CXCR4 protein; glycans; Human immunodeficiency virus 1; SDF-1 protein
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.1999.0033

We demonstrate that human immunodeficiency virus HIV-1LAI envelope glycoprotein 120 (gp120LAi) specifically interacts with several membrane ligands on lymphoid CEM or monocytic U937 cells in addition to its previously identified receptor, CD4, and CXCR4, its coreceptor. In its native state, gp120LAI is able to elicit specific multimolecular complexes with these membrane ligands at the surface of the cells; most of the interactions are abolished by mannan or heparin but not by dextran. Similarly, stromal cell-derived factor (SDF)-1α interacts not only with CXCR4 expressed by CXCR4+ CD4+ U937, CEM, and HOS-CD4+ CXCR4+ cells but also with CD4 expressed by intact U937, CEM, and HOS-CD4+ CXCR4+/− cells or electroblotted onto Immobilon. SDF-1α binding to CD4+ CXCR4+/− cells, or soluble CD4 electroblotted onto Immobilon, is significantly inhibited by sCD4, whereas truncated sCD4 lacking D3 and D4 domains had no significant effect, which indicates that SDF-1 binds to CD4 but at regions different from the HIV-gp120-binding site. Heparin and mannan also inhibit SDF-1α binding to intact CD4+ CXCR4+/− cells, and electroblotted soluble CD4. Heparitinase treatment of such cells reduced SDF-1α binding. These data demonstrate that glycans and glycosaminoglycans are directly or indirectly involved in the interactions of HIV-1 gp120LAI and of SDF-1α with membrane ligands of CD4+ CXCR4+ cells and thus could play a role both in HIV-1 infection and in the physiology of SDF-1α.