Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies

Nat Commun. 2015 Jun 24:6:7479. doi: 10.1038/ncomms8479.

Abstract

The envelope spike of HIV-1 employs a 'glycan shield' to protect itself from antibody-mediated neutralization. Paradoxically, however, potent broadly neutralizing antibodies (bnAbs) that target this shield have been isolated. The unusually high glycan density on the gp120 subunit limits processing during biosynthesis, leaving a region of under-processed oligomannose-type structures, which is a primary target of these bnAbs. Here we investigate the contribution of individual glycosylation sites in the formation of this so-called intrinsic mannose patch. Deletion of individual sites has a limited effect on the overall size of the intrinsic mannose patch but leads to changes in the processing of neighbouring glycans. These structural changes are largely tolerated by a panel of glycan-dependent bnAbs targeting these regions, indicating a degree of plasticity in their recognition. These results support the intrinsic mannose patch as a stable target for vaccine design.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Glycosylation
  • HEK293 Cells
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp120 / metabolism
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / metabolism
  • Humans
  • Mannose / immunology*
  • Mannose / metabolism
  • Mass Spectrometry
  • Mutagenesis, Site-Directed
  • Polysaccharides / immunology*

Substances

  • Antibodies, Neutralizing
  • HIV Envelope Protein gp120
  • Polysaccharides
  • Mannose