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
January 2002
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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.
- Humans
- Research Support, Non-U.S. Gov't
- Recombinant Fusion Proteins/genetics/metabolism
- Neutralization Tests
- *Antibody-Dependent Enhancement
- HIV Envelope Protein gp120/*chemistry/genetics/*metabolism
- HIV Infections/virology
- HIV-1/genetics/immunology/*pathogenicity
- Receptors, CCR5/*metabolism
- Receptors, CXCR4/metabolism
- antibody
- virus
- antibody-mediated enhancement
- enhancement
- coreceptor
- antibody-mediated
- entry
- immunodeficiency
- envelope
- infectivity
- 87.cd cells
- 16.4
- virol
- usage
- gp 120
- neutralization
- infection
- ccr 5
- domain
- v 3 loop
