Overview
Publication
Proc Natl Acad Sci U S A. 2008 Mar 11; 105(10):3739-44.
PubMed ID: 18322015
Title
A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies
Authors
Frey G, Peng H, Rits-Volloch S, Morelli M, Cheng Y, Chen B
Abstract
Most antibodies induced by HIV-1 are ineffective at preventing initiation or spread of infection because they are either nonneutralizing or narrowly isolate-specific. Rare, ""broadly neutralizing"" antibodies have been detected that recognize relatively conserved regions on the envelope glycoprotein. Using stringently characterized, homogeneous preparations of trimeric HIV-1 envelope protein in relevant conformations, we have analyzed the molecular mechanism of neutralization by two of these antibodies, 2F5 and 4E10. We find that their epitopes, in the membrane-proximal segment of the envelope protein ectodomain, are exposed only on a form designed to mimic an intermediate state during viral entry. These results help explain the rarity of 2F5- and 4E10-like antibody responses and suggest a strategy for eliciting them.
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