Publication Date:
2012-11-16
Description:
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 approximately 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Jinghe -- Ofek, Gilad -- Laub, Leo -- Louder, Mark K -- Doria-Rose, Nicole A -- Longo, Nancy S -- Imamichi, Hiromi -- Bailer, Robert T -- Chakrabarti, Bimal -- Sharma, Shailendra K -- Alam, S Munir -- Wang, Tao -- Yang, Yongping -- Zhang, Baoshan -- Migueles, Stephen A -- Wyatt, Richard -- Haynes, Barton F -- Kwong, Peter D -- Mascola, John R -- Connors, Mark -- HSN261200800001E/PHS HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2012 Nov 15;491(7424):406-12. doi: 10.1038/nature11544. Epub 2012 Sep 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23151583" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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