Distinct conformational states of HIV-1 gp41 are recognized by neutralizing and non-neutralizing antibodies

Gary Frey, Jia Chen, Sophia Rits-Volloch, Michael M. Freeman, Susan Zolla-Pazner, Bing Chen

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

HIV-1 envelope glycoprotein gp41 undergoes large conformational changes to drive fusion of viral and target cell membranes, adopting at least three distinct conformations during the viral entry process. Neutralizing antibodies against gp41 block HIV-1 infection by targeting gp41′s membrane-proximal external region in a fusion-intermediate state. Here we report biochemical and structural evidence that non-neutralizing antibodies, capable of binding with high affinity to an immunodominant segment adjacent to the neutralizing epitopes in the membrane-proximal region, recognize a gp41 conformation that exists only when membrane fusion is complete. We propose that these non-neutralizing antibodies are induced in HIV-1ginfected individuals by gp41 in a triggered, postfusion form and contribute to production of ineffective humoral responses. These results have important implications for gp41-based vaccine design.

Original languageEnglish
Pages (from-to)1486-1491
Number of pages6
JournalNature Structural and Molecular Biology
Volume17
Issue number12
DOIs
StatePublished - Dec 2010
Externally publishedYes

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