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

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

doi:10.1038/ncomms8479

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

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

Infectious Diseases

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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.

Original language	English
Article number	7479
Number of pages	11
Journal	Nature Communications
Volume	6
Issue number	1
Early online date	24 Jun 2015
DOIs	https://doi.org/10.1038/ncomms8479
Publication status	Published - 24 Jun 2015

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Glycan clustering stabilizes the_PRITCHARD_Online 13May2015_GREEN AAMAccepted author manuscript, 1.34 MB

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Pritchard, L. K., Spencer, D. I. R., Royle, L., Bonomelli, C., Seabright, G. E., Behrens, A.-J., Kulp, D. W., Menis, S., Krumm, S. A., Dunlop, D. C., Crispin, D. J., Bowden, T. A., Scanlan, C. N., Ward, A. B., Schief, W. R., Doores, K. J., & Crispin, M. (2015). Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies. Nature Communications, 6(1), Article 7479. https://doi.org/10.1038/ncomms8479

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

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.",

author = "Pritchard, {Laura K} and Spencer, {Daniel I R} and Louise Royle and Camille Bonomelli and Seabright, {Gemma E} and Anna-Janina Behrens and Kulp, {Daniel W} and Sergey Menis and Krumm, {Stefanie A} and Dunlop, {D Cameron} and Crispin, {Daniel J} and Bowden, {Thomas A} and Scanlan, {Christopher N} and Ward, {Andrew B} and Schief, {William R} and Doores, {Katie J} and Max Crispin",

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Pritchard, LK, Spencer, DIR, Royle, L, Bonomelli, C, Seabright, GE, Behrens, A-J, Kulp, DW, Menis, S, Krumm, SA, Dunlop, DC, Crispin, DJ, Bowden, TA, Scanlan, CN, Ward, AB, Schief, WR, Doores, KJ & Crispin, M 2015, 'Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies', Nature Communications, vol. 6, no. 1, 7479. https://doi.org/10.1038/ncomms8479

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T1 - Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies

AU - Pritchard, Laura K

AU - Spencer, Daniel I R

AU - Royle, Louise

AU - Bonomelli, Camille

AU - Seabright, Gemma E

AU - Behrens, Anna-Janina

AU - Kulp, Daniel W

AU - Menis, Sergey

AU - Krumm, Stefanie A

AU - Dunlop, D Cameron

AU - Crispin, Daniel J

AU - Bowden, Thomas A

AU - Scanlan, Christopher N

AU - Ward, Andrew B

AU - Schief, William R

AU - Doores, Katie J

AU - Crispin, Max

PY - 2015/6/24

Y1 - 2015/6/24

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms8479

DO - 10.1038/ncomms8479

M3 - Article

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SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7479

ER -

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

Abstract

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