Characterization of CD4-induced epitopes on the HIV type 1 gp120 envelope glycoprotein recognized by neutralizing human monoclonal antibodies

AIDS Res Hum Retroviruses. 2002 Nov 1;18(16):1207-17. doi: 10.1089/08892220260387959.

Abstract

The entry of human immunodeficiency virus (HIV-1) into target cells typically requires the sequential binding of the viral exterior envelope glycoprotein, gp120, to CD4 and a chemokine receptor. CD4 binding exposes gp120 epitopes recognized by CD4-induced (CD4i) antibodies, which can block virus binding to the chemokine receptor. We identified three new CD4i antibodies from an HIV-1-infected individual and localized their epitopes. These epitopes include a highly conserved gp120 beta-strand encompassing residues 419-424, which is also important for binding to the CCR5 chemokine receptor. All of the CD4i antibodies inhibited the binding of gp120-CD4 complexes to CCR5. CD4i antibodies and CD4 reciprocally induced each other's binding, suggesting that these ligands recognize a similar gp120 conformation. The CD4i antibodies neutralized laboratory-adapted HIV-1 isolates; primary isolates were more resistant to neutralization by these antibodies. Thus, all known CD4i antibodies recognize a common, conserved gp120 element overlapping the binding site for the CCR5 chemokine receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • CD4 Antigens / immunology*
  • Cell Line
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology*
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / immunology*
  • HIV-1 / immunology*
  • Humans
  • Neutralization Tests
  • Protein Conformation

Substances

  • Antibodies, Monoclonal
  • CD4 Antigens
  • Epitopes
  • HIV Envelope Protein gp120