Nature (London), 2012-11, Vol.491 (7424), p.406-412
2012
Details
- Autor(en) / Beteiligte
- Titel
- Broad and potent neutralization of HIV―1 by a gp41―specific human antibody
- Ist Teil von
- Nature (London), 2012-11, Vol.491 (7424), p.406-412
- Ort / Verlag
- London: Nature Publishing Group
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- Psychology & Behavioral Sciences Collection
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836, 1476-4687eISSN: 1476-4687DOI: 10.1038/nature11544Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4854285
- Format
- –
- Schlagworte
- Amino Acid Substitution, Analytical, structural and metabolic biochemistry, Antibodies, Antibodies, Neutralizing - chemistry, Antibodies, Neutralizing - metabolism, Antibody Specificity, Biological and medical sciences, Cell culture, Cells, Cultured, Crystal structure, Flow cytometry, Fundamental and applied biological sciences. Psychology, HEK293 Cells, HIV Antibodies - chemistry, HIV Antibodies - isolation & purification, HIV Antibodies - metabolism, HIV Envelope Protein gp41 - chemistry, HIV Envelope Protein gp41 - immunology, HIV infection, HIV-1 - physiology, Human immunodeficiency virus 1, Humans, Lipids, Models, Molecular, Molecular and cellular biology, Molecular Sequence Data, Peptides, Prevention, Product development, Properties, Protein Binding, Protein Structure, Tertiary, Vaccines, Viral antibodies