Polyionic Compounds Selectively Alter Availability of CD4 Receptors for HIV Coat Protein rgp 120
We studied the ability of several polyionic compounds, previously shown to have anti-HIV activity in vitro, 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 (ATA) could completely inhibit binding of anti-CD4 (Leu 3a) 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 rgp 120 by Evans Blue or aurin tricarboxylic acid. Using our developed flow cytometric method we could detect novel compounds which can prevent binding of rgp120 specifically and have good anti-HIV activity.
We have also found that ATA prevents the binding of interferon-α to its receptor in a dose dependent manner (12–50 µM range). Membrane potential shift, associated with the binding of interferon-α to its receptor, was also blocked by ATA in a dose dependent fashion. Several other agents, able to prevent the binding of rgp120 to the CD4 molecule, did not block the binding of interferon-α to its receptor. Our results indicate that potential anti-AIDS drugs should be screened for such undesired side effects.
KeywordsEvans Blue Dextran Sulfate Evans Blue Dextran Sulfate Daudi Cell
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- 4.Schols D, Baba M, Pauwels R and De Clercq E, Flow cytometric method to demonstrate whether anti-HIV-1 agents inhibit virion binding to T4+ cells. J. Acq. 1mm. Def. Synd. 2: 10–15, 1989.Google Scholar
- 5.Mizumoto K, Sugawara I, Ito W, Kodama T, Hayami M and Mori S, Sulfated homopolysaccharides with immunomodulating activities are more potent anti-HTLV-IH agents than sulfated heteropolysaccharides, Japan J. Exp. Med. 58: 145–151, 1988.Google Scholar
- 8.Balzarini J, Mitsuya H, De Clercq E and Broder S, Aurintricarboxylic acid and Evans Blue represent two different classes of anionic compounds which selectively inhibit the cytopathogenicity of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus. Biochem. Biophys. Res. Commun. 136: 64–71, 1986.PubMedCrossRefGoogle Scholar
- 9.Balzarini J, Mitsuya H, De Clercq E and Broder S, Comparative inhibitory effects of suramin and other selected compounds on the infectivity and replication of human T-cell lymphotrophic virus (HTLV-IH)/lymphadenopathy-associated virus (LAV). Int. J. Cancer 37: 451–457, 1986.PubMedCrossRefGoogle Scholar
- 15.McDougal JS, Nicholson JKA, Cross GD, Cort SP, Kennedy MS and Mawle AC, Binding of the human retrovirus HTLV-III/LAC/ARV/HIV the CD4 (T4) molecule; conformation dependence, epitope mapping, antibody inhibition, and potential for idiotype mimicry. J. Immunol. 137: 2937–2944, 1986.PubMedGoogle Scholar