A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies.

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.
Authors	Gary Frey, Hanqin Peng, Sophia Rits-Volloch, Marco Morelli, Yifan Cheng, Bing Chen
Journal	Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 105 Issue 10 Pg. 3739-44 (Mar 11 2008) ISSN: 1091-6490 [Electronic] United States
PMID	18322015 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antibodies, Monoclonal HIV Antibodies HIV Antigens HIV Envelope Protein gp41 Ligands Recombinant Fusion Proteins env Gene Products, Human Immunodeficiency Virus gp140 envelope protein, Human immunodeficiency virus 1
Topics	Antibodies, Monoclonal (immunology) Binding Sites, Antibody HIV Antibodies (immunology) HIV Antigens (immunology) HIV Envelope Protein gp41 (chemistry, immunology) HIV-1 (immunology) Kinetics Ligands Neutralization Tests Protein Structure, Quaternary Protein Structure, Secondary Recombinant Fusion Proteins (chemistry, immunology) Surface Plasmon Resonance env Gene Products, Human Immunodeficiency Virus (chemistry)

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