Antibody-mediated enhancement of human immunodeficiency virus type 1 infectivity is determined by the structure of gp120 and depends on modulation of the gp120-CCR5 interaction

J Virol. 2002 Mar;76(6):2827-34. doi: 10.1128/jvi.76.6.2827-2834.2002.

Abstract

In this study, we characterized the viral determinants of coreceptor usage in relation to susceptibility to antibody-mediated neutralization or enhancement of infectivity by using chimeras of three highly related human immunodeficiency virus type 1 (HIV-1) isolates of different phenotypes. We found that the V3 region was the main determinant of antibody-mediated enhancement and coreceptor specificity but that the overall structure of gp120 was also important for these properties. Constructs susceptible to antibody-mediated enhancement preferentially use CCR5 as a coreceptor, in contrast to constructs that were neutralized or not affected. Using monoclonal antibodies directed against CD4 or CCR5, we were able to show that antibody-mediated enhancement was CD4 dependent. Altogether, our results suggest that the modulation of the interaction of gp120 with CCR5 is the mechanism underlying antibody-mediated enhancement of HIV-1 infectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody-Dependent Enhancement*
  • HIV Envelope Protein gp120 / chemistry*
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / metabolism*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / pathogenicity*
  • Humans
  • Neutralization Tests
  • Receptors, CCR5 / metabolism*
  • Receptors, CXCR4 / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • HIV Envelope Protein gp120
  • Receptors, CCR5
  • Receptors, CXCR4
  • Recombinant Fusion Proteins