Two immunodominant domains of gp41 bind antibodies which enhance human immunodeficiency virus type 1 infection in vitro

J Virol. 1991 Aug;65(8):4169-76. doi: 10.1128/JVI.65.8.4169-4176.1991.

Abstract

Four of eight human monoclonal antibodies (huMAbs) to gp41 were identified which could enhance human immunodeficiency virus type 1 (HIV-1) infection in vitro by complement-mediated antibody-dependent enhancement (C'-ADE). These enhancing huMAbs were mapped to two distinct domains on the HIV-1 gp41 transmembrane glycoprotein by using synthetic peptides. The first domain, amino acids 579 to 613 (peptide AA579-613), was recognized by three of the four enhancing huMAbs. The AA579-613 peptide blocked C'-ADE of HIV-1 infection in vitro whether it was mediated by these three huMAbs or by human polyclonal anti-HIV serum. The second domain, amino acids 644 to 663, bound the remaining enhancing huMAb. This peptide weakly blocked C'-ADE mediated by the huMAb and by an HIV immune globulin fraction but did not block C'-ADE mediated by a patient's serum. The patient's serum did react with the peptide in an enzyme immunoassay. The huMAbs to the two domains could interact in vitro to enhance HIV-1 infection in a synergistic manner. These two domains, which bind enhancing antibodies, are conserved between HIV-1 isolates as well as between HIV-2 and simian immunodeficiency virus isolates. These data demonstrate the existence of two conserved regions within the HIV-1 gp41 which bind enhancing antibodies; these two domains, amino acids 579 to 613 and 644 to 663, may prove important in HIV-1 vaccine development and in immunopathogenesis of HIV-1 infection.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / immunology*
  • Binding, Competitive
  • Cell Line
  • Complement System Proteins / immunology*
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • HIV Antibodies / immunology*
  • HIV Antibodies / metabolism
  • HIV Envelope Protein gp41 / chemistry
  • HIV Envelope Protein gp41 / immunology*
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / immunology

Substances

  • Antibodies, Monoclonal
  • HIV Antibodies
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • Complement System Proteins