Polyionic compounds selectively alter availability of CD4 receptors for HIV coat protein rgp120.
We studied the ability of several polyionic compounds, previously shown to have activity in vitro against human immunodeficiency virus (anti-HIV) to block binding of anti-CD4 and recombinant HIV gp120 to the CD4 receptor on human lymphocytes. We found that Evans blue and aurin tricarboxylic acid could completely inhibit binding of anti-CD4 (Leu3a) and rgp120 and have selectivity for the CD4 receptor. A number of other compounds, including dextran sulfate and heparin had no effect on binding of rgp120 and were shown to be nonspecific for inhibition of binding of monoclonal antibodies to different T-cell receptors. Studies using a number of membrane-active drugs showed that changes in membrane potential or ion fluxes were not involved in the inhibition of binding of rgp120 by Evans blue or aurin tricarboxylic acid.
Weaver
J L
JL
Food and Drug Administration, Washington, DC 20204.
Gergely
P
P
Pine
P S
PS
Patzer
E
E
Aszalos
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000382:microbiology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016264:Dextran Sulfate / Q000494:pharmacology*; D005070:Evans Blue / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013858:Thiobarbiturates / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D013858:Thiobarbiturates; D001312:Aurintricarboxylic Acid; D005070:Evans Blue; C025284:bis(1,3-diethylthiobarbiturate)trimethineoxonol; D016264:Dextran Sulfate; D002118:Calcium