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Composition and antigenic effects of individual glycan sites of a trimeric HIV-1 envelope glycoprotein

Composition and antigenic effects of individual glycan sites of a trimeric HIV-1 envelope glycoprotein
Composition and antigenic effects of individual glycan sites of a trimeric HIV-1 envelope glycoprotein

The HIV-1 envelope glycoprotein trimer is covered by an array of N-linked glycans that shield it from immune surveillance. The high density of glycans on the trimer surface imposes steric constraints limiting the actions of glycan-processing enzymes, so that multiple under-processed structures remain on specific areas. These oligomannose glycans are recognized by broadly neutralizing antibodies (bNAbs) that are not thwarted by the glycan shield but, paradoxically, target it. Our site-specific glycosylation analysis of a soluble, recombinant trimer (BG505 SOSIP.664) maps the extremes of simplicity and diversity of glycan processing at individual sites and reveals a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, we identify examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens.

2211-1247
2695-2706
Behrens, Anna Janina
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Vasiljevic, Snezana
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Pritchard, Laura K.
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Harvey, David J.
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Andev, Rajinder S.
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Krumm, Stefanie A.
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Struwe, Weston B.
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Cupo, Albert
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Kumar, Abhinav
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Zitzmann, Nicole
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Seabright, Gemma E.
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Kramer, Holger B.
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Spencer, Daniel I.R.
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Royle, Louise
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Lee, Jeong Hyun
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Klasse, Per J.
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Burton, Dennis R.
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Wilson, Ian A.
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Ward, Andrew B.
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Sanders, Rogier W.
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Moore, John P.
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Doores, Katie J.
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Crispin, Max
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Behrens, Anna Janina
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Vasiljevic, Snezana
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Pritchard, Laura K.
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Harvey, David J.
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Andev, Rajinder S.
067379bf-c777-4d51-b04b-a229f1323836
Krumm, Stefanie A.
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Struwe, Weston B.
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Cupo, Albert
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Kumar, Abhinav
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Zitzmann, Nicole
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Seabright, Gemma E.
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Kramer, Holger B.
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Spencer, Daniel I.R.
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Royle, Louise
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Lee, Jeong Hyun
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Klasse, Per J.
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Burton, Dennis R.
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Wilson, Ian A.
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Ward, Andrew B.
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Sanders, Rogier W.
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Moore, John P.
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Doores, Katie J.
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Crispin, Max
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Behrens, Anna Janina, Vasiljevic, Snezana, Pritchard, Laura K., Harvey, David J., Andev, Rajinder S., Krumm, Stefanie A., Struwe, Weston B., Cupo, Albert, Kumar, Abhinav, Zitzmann, Nicole, Seabright, Gemma E., Kramer, Holger B., Spencer, Daniel I.R., Royle, Louise, Lee, Jeong Hyun, Klasse, Per J., Burton, Dennis R., Wilson, Ian A., Ward, Andrew B., Sanders, Rogier W., Moore, John P., Doores, Katie J. and Crispin, Max (2016) Composition and antigenic effects of individual glycan sites of a trimeric HIV-1 envelope glycoprotein. Cell Reports, 14 (11), 2695-2706. (doi:10.1016/j.celrep.2016.02.058).

Record type: Article

Abstract

The HIV-1 envelope glycoprotein trimer is covered by an array of N-linked glycans that shield it from immune surveillance. The high density of glycans on the trimer surface imposes steric constraints limiting the actions of glycan-processing enzymes, so that multiple under-processed structures remain on specific areas. These oligomannose glycans are recognized by broadly neutralizing antibodies (bNAbs) that are not thwarted by the glycan shield but, paradoxically, target it. Our site-specific glycosylation analysis of a soluble, recombinant trimer (BG505 SOSIP.664) maps the extremes of simplicity and diversity of glycan processing at individual sites and reveals a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, we identify examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens.

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Accepted/In Press date: 10 February 2016
e-pub ahead of print date: 10 March 2016
Published date: 22 March 2016

Identifiers

Local EPrints ID: 414326
URI: http://eprints.soton.ac.uk/id/eprint/414326
ISSN: 2211-1247
PURE UUID: 2c003109-85c5-4664-9060-1064d75fafaa
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

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Date deposited: 26 Sep 2017 16:30
Last modified: 15 Jan 2020 17:49

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Contributors

Author: Anna Janina Behrens
Author: Snezana Vasiljevic
Author: Laura K. Pritchard
Author: David J. Harvey
Author: Rajinder S. Andev
Author: Stefanie A. Krumm
Author: Weston B. Struwe
Author: Albert Cupo
Author: Abhinav Kumar
Author: Nicole Zitzmann
Author: Gemma E. Seabright
Author: Holger B. Kramer
Author: Daniel I.R. Spencer
Author: Louise Royle
Author: Jeong Hyun Lee
Author: Per J. Klasse
Author: Dennis R. Burton
Author: Ian A. Wilson
Author: Andrew B. Ward
Author: Rogier W. Sanders
Author: John P. Moore
Author: Katie J. Doores
Author: Max Crispin ORCID iD

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