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

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

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.

Pritchard, Laura K.
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Spencer, Daniel I.R.
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Royle, Louise
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Bonomelli, Camille
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Seabright, Gemma E.
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Behrens, Anna Janina
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Kulp, Daniel W.
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Menis, Sergey
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Krumm, Stefanie A.
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Dunlop, D. Cameron
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Crispin, Daniel J.
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Bowden, Thomas A.
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Scanlan, Christopher N.
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Ward, Andrew B.
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Schief, William R.
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Doores, Katie J.
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Crispin, Max
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Pritchard, Laura K.
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Spencer, Daniel I.R.
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Royle, Louise
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Bonomelli, Camille
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Seabright, Gemma E.
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Behrens, Anna Janina
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Kulp, Daniel W.
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Menis, Sergey
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Krumm, Stefanie A.
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Dunlop, D. Cameron
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Crispin, Daniel J.
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Bowden, Thomas A.
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Scanlan, Christopher N.
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Ward, Andrew B.
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Schief, William R.
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Doores, Katie J.
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Crispin, Max
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Pritchard, Laura K., Spencer, Daniel I.R., Royle, Louise, Bonomelli, Camille, Seabright, Gemma E., Behrens, Anna Janina, Kulp, Daniel W., Menis, Sergey, Krumm, Stefanie A., Dunlop, D. Cameron, Crispin, Daniel J., Bowden, Thomas A., Scanlan, Christopher N., Ward, Andrew B., Schief, William R., Doores, Katie J. and Crispin, Max (2015) Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies. Nature Communications, 6, [7449]. (doi:10.1038/ncomms8479).

Record type: Article

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.

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More information

Accepted/In Press date: 13 May 2015
e-pub ahead of print date: 24 June 2015
Published date: 24 June 2015

Identifiers

Local EPrints ID: 414319
URI: http://eprints.soton.ac.uk/id/eprint/414319
PURE UUID: dea9862f-05a0-4603-83e9-842f5eeebed8
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 26 Sep 2017 16:30
Last modified: 06 Jun 2024 01:59

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Contributors

Author: Laura K. Pritchard
Author: Daniel I.R. Spencer
Author: Louise Royle
Author: Camille Bonomelli
Author: Gemma E. Seabright
Author: Anna Janina Behrens
Author: Daniel W. Kulp
Author: Sergey Menis
Author: Stefanie A. Krumm
Author: D. Cameron Dunlop
Author: Daniel J. Crispin
Author: Thomas A. Bowden
Author: Christopher N. Scanlan
Author: Andrew B. Ward
Author: William R. Schief
Author: Katie J. Doores
Author: Max Crispin ORCID iD

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