Specific interaction of aurintricarboxylic acid with the human immunodeficiency virus/CD4 cell receptor.
The triphenylmethane derivative aurintricarboxylic acid (ATA), but not aurin, selectively prevented the binding of OKT4A/Leu-3a monoclonal antibody (mAb) and, to a lesser extent, OKT4 mAb to the CD4 cell receptor for human immunodeficiency virus type 1 (HIV-1). The effect was seen within 1 min at an ATA concentration of 10 microM in various T4+ cells (MT-4, U-937, peripheral blood lymphocytes, and monocytes). It was dose-dependent and reversible. ATA prevented the attachment of radiolabeled HIV-1 particles to MT-4 cells, which could be expected as the result of its specific binding to the HIV/CD4 receptor. Other HIV inhibitors such as suramin, fuchsin acid, azidothymidine, dextran sulfate, heparin, and pentosan polysulfate did not affect OKT4A/Leu-3a mAb binding to the CD4 receptor, although the sulfated polysaccharides suppressed HIV-1 adsorption to the cells at concentrations required for complete protection against HIV-1 cytopathogenicity. Thus, ATA is a selective marker molecule for the CD4 receptor. ATA also interfered with the staining of membrane-associated HIV-1 glycoprotein gp120 by a mAb against it. These unusual properties of a small molecule of nonimmunological origin may have important implications for the study of CD4/HIV/AIDS pathogenesis and possibly treatment.
Schols
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Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Baba
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M
Pauwels
R
R
Desmyter
J
J
De Clercq
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E
D000327:Adsorption; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015699:HIV Envelope Protein gp120; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015728:Receptors, HIV; D011990:Receptors, Transferrin / Q000187:drug effects; D011991:Receptors, Virus / Q000187:drug effects / Q000276:immunology*; D012191:Retroviridae Proteins / Q000032:analysis
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D003509:Cyclohexanecarboxylic Acids; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV; D011990:Receptors, Transferrin; D011991:Receptors, Virus; D012191:Retroviridae Proteins; D001312:Aurintricarboxylic Acid