Characterization of gp120 Binding to the CD4 Antigen and Detection of Specific Inhibitors

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Abstract
The first step in the attack of human immunodeficiency virus (HIV-1) on human T lymphocytes is binding of the viral coat protein, gp120, to the CD4 antigen on the surface of the cells. The present study examines 125I-gp120 binding to CEM and U937 cells. The results of this study show that this process is more complex than previously thought, consisting of multiple binding components, some of which may reflect processes occurring after the actual binding. Despite its complexity, measurement of the inhibition of 125I-gp120 binding by monoclonal antibodies to the CD4 antigen or to gp120 generally parallels direct measurement of the inhibition of HIV-1 binding to cells expressing the CD4 antigen (CD4 positive). Furthermore, aurintricarboxylic acid and pentosan polysulphate, inhibitors of the association of HIV-1 with cells, also inhibit 125I-gp120 binding. This is the first case in which a small molecule has been shown to inhibit gp120 binding using a classical radioligand binding assay. Two other inhibitors of HIV-1 association with cells, dextran sulphate and chondroitin sulphate, were less effective as 125I-gp120 binding inhibitors, suggesting that prevention HIV-1/cell association can be produced by mechanisms other than direct inhibition of gp120/CD4 binding.