Binding to CD4 of synthetic peptides patterned on the principal neutralizing domain of the HIV-1 envelope protein.

Abstract

The interaction between the viral envelope protein gp120 and the cellular surface antigen CD4 is a key event in HIV-1 infection. Reciprocal high affinity binding sites have been located in the first domain of CD4 and in the carboxy-terminal region of gp120, respectively. Upon infection, the membranes of the target cells fuse; sites of CD4 and gp120, distinct from their high affinity binding sites, play a role in the post-binding events leading to syncytia formation. We have studied the interactions of CD4 with gp120 and gp120-derived peptides using an in vitro assay based on immobilized recombinant soluble CD4 (sCD4). In this system CD4 binds to recombinant soluble gp120 and to anti-receptor peptides derived from the high affinity CD4-binding site of gp120, as well as to peptides corresponding to the principal neutralizing domain (PND) of the envelope protein, i.e., to the domain required for HIV-1-mediated syncytium formation. Competition experiments performed using epitope-specific mAbs and a variety of peptides indicated that PND-derived peptides are specifically recognized by a CD4 site adjacent to, but distinct from, the high affinity gp120-binding site of CD4. Synthetic peptides patterned on the PND of different viral isolates were retained onto sCD4-based affinity columns at different extent; some of the structural requirements for binding were analyzed. Studies performed on CD4+ T-cells showed that PND-derived peptides also interact with CD4 in its native membrane-bound conformation. These results indicate that a direct contact takes place between CD4 and the gp120 domain participating in HIV-induced syncytia formation.

Statistics

0200400600800'94'97'00'03'06'09'12'15
Citations per Year

271 Citations

Semantic Scholar estimates that this publication has 271 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Autiero1991BindingTC, title={Binding to CD4 of synthetic peptides patterned on the principal neutralizing domain of the HIV-1 envelope protein.}, author={Monica Autiero and Paolo Abrescia and Monica Dettin and Carlo Di Bello and John Guardiola}, journal={Virology}, year={1991}, volume={185 2}, pages={820-8} }