Dextran sulfate and other polyanionic anti-HIV compounds specifically interact with the viral gp120 glycoprotein expressed by T-cells persistently infected with HIV-1.
Eighty to 100% of persistently HIV-1-infected HUT-78 cells express the viral glycoprotein gp120 as demonstrated with anti-gp 120 monoclonal antibody (mAb) and fluorescence-activated cell sorter (FACS) analysis. Several polyanionic anti-HIV compounds, i.e., dextran sulfate, pentosan polysulfate, heparin, aurintricarboxylic acid (ATA), suramin, and Evans blue, which are known to inhibit the adsorption of HIV particles to CD4+ cells, prevented the binding of anti-gp120 mAb to the persistently HIV-1 infected HUT-78 cells. This effect was dose-dependent and reversible. Except for ATA, the polyanionic compounds did not interfere with the binding of Leu3a/OKT4A mAB, indicating that they do not directly bind to the CD4 receptor. Thus, the inhibitory effect of dextran sulfate and its congeners on the interaction of the HIV gp120 with the cellular CD4 receptor can be ascribed to a specific binding ("shielding") of gp120.
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
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Schols
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Pauwels
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Desmyter
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De Clercq
D000911:Antibodies, Monoclonal / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology*; D001312:Aurintricarboxylic Acid / Q000378:metabolism / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology*; D002460:Cell Line; D002469:Cell Separation; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005070:Evans Blue / Q000378:metabolism / Q000494:pharmacology; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D010426:Pentosan Sulfuric Polyester / Q000378:metabolism / Q000494:pharmacology; D013498:Suramin / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D003911:Dextrans; D015699:HIV Envelope Protein gp120; D010426:Pentosan Sulfuric Polyester; D001312:Aurintricarboxylic Acid; D005070:Evans Blue; D013498:Suramin; D006493:Heparin; D016264:Dextran Sulfate