Short synthetic peptides derived from viral proteins compete with HIV gp120 for the binding to CD4 receptors

In the complex mechanism of adhesion, internalization, and infection of cel ls by human immunodeficiency virus (HIV) viral particles, a determinant rol e is played by the viral envelope glycoprotein gp120, which binds to CD4 re ceptors of T cells and monocytes. We tested the ability of a panel of 7- to 12-residue synthetic peptides, selected from the region 414-434 of the HIV -1 gp120, to inhibit the binding of the viral protein to CD4 receptors of c ultured human lymphoid cells. The assay was based on the observation that t he binding of gp120 to the receptors interferes with the binding of a speci fic anti-CD4 monoclonal antibody, as a result of the masking of the antibod y epitope; thus, we tested whether preincubation of cells with the peptides before gp120 addition might restore the recognition of the CD4 molecule by the antibody. High expression of CD4 receptors was thus assumed as indicat ion that the binding of the viral protein had been inhibited. Maximum activ ity was displayed by a 9-residue peptide located near the amino terminal en d of the 414-434 fragment. In addition, several fragments deduced from othe r viral proteins, possessing partial amino acid sequence homology with the HIV gp120 fragment, exhibited a similar type of interaction with the CD4 re ceptor. All active peptides contain the Cys residue (position 423 of gp120) . This residue is essential, although not sufficient, for inhibiting gp120 binding, as few other amino acid residues within the fragment play a comple mentary role in increasing or decreasing the inhibitory ability.