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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.

SUBMITTER: Frey G

PROVIDER: S-EPMC2268799 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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

Frey Gary G Peng Hanqin H Rits-Volloch Sophia S Morelli Marco M Cheng Yifan Y Chen Bing B

Proceedings of the National Academy of Sciences of the United States of America 20080305 10

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 antib ...[more]

PMID: 18322015

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