We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites.
- Authors
Kwong, Peter D; Doyle, Michael L; Casper, David J; Cicala, Claudia; Leavitt, Stephanie A; Majeed, Shahzad; Steenbeke, Tavis D; Venturi, Miro; Chaiken, Irwin; Fung, Michael; Katinger, Hermann; Parren, Paul W I H; Robinson, James; Van Ryk, Donald; Wang, Liping; Burton, Dennis R; Freire, Ernesto; Wyatt, Richard; Sodroski, Joseph; Hendrickson, Wayne A; Arthos, James
- Abstract
The ability of human immunodeficiency virus (HIV-1) to persist and cause AIDS is dependent on its avoidance of antibody-mediated neutralization. The virus elicits abundant, envelope-directed antibodies that have little neutralization capacity. This lack of neutralization is paradoxical, given the functional conservation and exposure of receptor-binding sites on the gp120 envelope glycoprotein, which are larger than the typical antibody footprint and should therefore be accessible for antibody binding. Because gp120-receptor interactions involve conformational reorganization, we measured the entropies of binding for 20 gp120-reactive antibodies. Here we show that recognition by receptor-binding-site antibodies induces conformational change. Correlation with neutralization potency and analysis of receptor-antibody thermodynamic cycles suggested a receptor-binding-site 'conformational masking' mechanism of neutralization escape. To understand how such an escape mechanism would be compatible with virus-receptor interactions, we tested a soluble dodecameric receptor molecule and found that it neutralized primary HIV-1 isolates with great potency, showing that simultaneous binding of viral envelope glycoproteins by multiple receptors creates sufficient avidity to compensate for such masking. Because this solution is available for cell-surface receptors but not for most antibodies, conformational masking enables HIV-1 to maintain receptor binding and simultaneously to resist neutralization.
- Publication
Nature, 2002, Vol 420, Issue 6916, p678
- ISSN
0028-0836
- Publication type
Journal Article
- DOI
10.1038/nature01188