Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein

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

doi:https://doi.org/10.1016/j.celrep.2016.02.058

Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein

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

Research output: Contribution to journal › Article › Academic › peer-review

204 Citations (Scopus)

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

Original language	English
Pages (from-to)	2695-2706
Journal	Cell reports
Volume	14
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2016.02.058
Publication status	Published - 2016

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https://doi.org/10.1016/j.celrep.2016.02.058

Cite this

Behrens, A.-J., Vasiljevic, S., Pritchard, L. K., Harvey, D. J., Andev, R. S., Krumm, S. A., Struwe, W. B., Cupo, A., Kumar, A., Zitzmann, N., Seabright, G. E., Kramer, H. B., Spencer, D. I. R., Royle, L., Lee, J. H., Klasse, P. J., Burton, D. R., Wilson, I. A., Ward, A. B., ... Crispin, M. (2016). Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein. Cell reports, 14(11), 2695-2706. https://doi.org/10.1016/j.celrep.2016.02.058

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title = "Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein",

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",

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

year = "2016",

doi = "https://doi.org/10.1016/j.celrep.2016.02.058",

language = "English",

volume = "14",

pages = "2695--2706",

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Behrens, A-J, Vasiljevic, S, Pritchard, LK, Harvey, DJ, Andev, RS, Krumm, SA, Struwe, WB, Cupo, A, Kumar, A, Zitzmann, N, Seabright, GE, Kramer, HB, Spencer, DIR, Royle, L, Lee, JH, Klasse, PJ, Burton, DR, Wilson, IA, Ward, AB, Sanders, RW, Moore, JP, Doores, KJ & Crispin, M 2016, 'Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein', Cell reports, vol. 14, no. 11, pp. 2695-2706. https://doi.org/10.1016/j.celrep.2016.02.058

TY - JOUR

T1 - Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein

AU - Behrens, Anna-Janina

AU - Vasiljevic, Snezana

AU - Pritchard, Laura K.

AU - Harvey, David J.

AU - Andev, Rajinder S.

AU - Krumm, Stefanie A.

AU - Struwe, Weston B.

AU - Cupo, Albert

AU - Kumar, Abhinav

AU - Zitzmann, Nicole

AU - Seabright, Gemma E.

AU - Kramer, Holger B.

AU - Spencer, Daniel I. R.

AU - Royle, Louise

AU - Lee, Jeong Hyun

AU - Klasse, Per J.

AU - Burton, Dennis R.

AU - Wilson, Ian A.

AU - Ward, Andrew B.

AU - Sanders, Rogier W.

AU - Moore, John P.

AU - Doores, Katie J.

AU - Crispin, Max

PY - 2016

Y1 - 2016

N2 - 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

AB - 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

U2 - https://doi.org/10.1016/j.celrep.2016.02.058

DO - https://doi.org/10.1016/j.celrep.2016.02.058

M3 - Article

C2 - 26972002

SN - 2211-1247

VL - 14

SP - 2695

EP - 2706

JO - Cell reports

JF - Cell reports

IS - 11

ER -