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Broad and potent neutralization of hiv-1 by a gp41-specific human antibody

Academic Article
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Overview

authors

  • Huang, J. H.
  • Ofek, G.
  • Laub, L.
  • Louder, M. K.
  • Doria-Rose, N. A.
  • Longo, N. S.
  • Imamichi, H.
  • Bailer, R. T.
  • Chakrabarti, Bimal
  • Sharma, S. K.
  • Alam, S. M.
  • Wang, T.
  • Yang, Y. P.
  • Zhang, B. S.
  • Migueles, S. A.
  • Wyatt, Richard
  • Haynes, B. F.
  • Kwong, P. D.
  • Mascola, J. R.
  • Connors, M.

publication date

  • November 2012

journal

  • Nature  Journal

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.

subject areas

  • Amino Acid Substitution
  • Antibodies, Neutralizing
  • Antibody Specificity
  • Cells, Cultured
  • HEK293 Cells
  • HIV Antibodies
  • HIV Envelope Protein gp41
  • HIV-1
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
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Identity

PubMed Central ID

  • PMC4854285

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature11544

PubMed ID

  • 23151583
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Additional Document Info

start page

  • 406

end page

  • 12

volume

  • 491

issue

  • 7424

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