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| Article Authors: | Jinghe Huang; Gilad Ofek; Leo Laub; Mark K Louder; Nicole A Doria-Rose; Nancy S Longo; Hiromi Imamichi; Robert T Bailer; Bimal Chakrabarti; Shailendra K Sharma; S Munir Alam; Tao Wang; Yongping Yang; Baoshan Zhang; Stephen A Migueles; Richard Wyatt; Barton F Haynes; Peter D Kwong; John R Mascola; Mark Connors |
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| Article Title: | Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. |
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| Reference ID: | 1025379 |
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| Abstract: | Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein. |
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| Affiliations: | HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. |
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| Date: | 2012 |
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| Reference Type: | Literature |
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| PubMed ID: | 23151583 |
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| Journal: | Nature |
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| Journal Volume: | 491 |
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| Article Pages: | 406-12 |
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| Journal ISSN: | 1476-4687 |
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| Article Chemical List: | Antibodies, Neutralizing;HIV Antibodies;HIV Envelope Protein gp41 |
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| Article MeSH List: | Amino Acid Substitution; Antibodies, Neutralizing(chemistry; metabolism); Antibody Specificity; Cells, Cultured; HEK293 Cells; HIV Antibodies(chemistry; isolation & purification; metabolism); HIV Envelope Protein gp41(chemistry; immunology); HIV-1(physiology); Humans; Models, Molecular; Molecular Sequence Data; Protein Binding; Protein Structure, Tertiary |
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| Curation Last Updated: | 2013-05-11 20:08:50 |
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