title: 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.
authors.affiliation: International Institute of Genetics and Biophysics, CNR, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Autiero
authors.forename: P
authors.initials: P
authors.lastname: Abrescia
authors.forename: M
authors.initials: M
authors.lastname: Dettin
authors.forename: C
authors.initials: C
authors.lastname: Di Bello
authors.forename: J
authors.initials: J
authors.lastname: Guardiola
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000502:physiology; D015704:CD4 Antigens / Q000378:metabolism*; D002459:Cell Fusion / Q000502:physiology; D002460:Cell Line; D002846:Chromatography, Affinity; D000939:Epitopes / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D011869:Radioligand Assay
chemical_list: D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments