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 pr...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Publishing Group
2015
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| _version_ | 1797067508898856960 |
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| author | Pritchard, L Spencer, D Royle, L Bonomelli, C Seabright, G Behrens, A Kulp, D Menis, S Krumm, S Dunlop, D Crispin, D Bowden, T Scanlan, C Ward, A Schief, W Doores, K Crispin, M |
| author_facet | Pritchard, L Spencer, D Royle, L Bonomelli, C Seabright, G Behrens, A Kulp, D Menis, S Krumm, S Dunlop, D Crispin, D Bowden, T Scanlan, C Ward, A Schief, W Doores, K Crispin, M |
| author_sort | Pritchard, L |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:57:18Z |
| format | Journal article |
| id | oxford-uuid:4d5b02a9-32c4-491f-9272-a06415e5cdf8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:57:18Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:4d5b02a9-32c4-491f-9272-a06415e5cdf82022-03-26T15:55:04ZGlycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4d5b02a9-32c4-491f-9272-a06415e5cdf8EnglishSymplectic Elements at OxfordNature Publishing Group2015Pritchard, LSpencer, DRoyle, LBonomelli, CSeabright, GBehrens, AKulp, DMenis, SKrumm, SDunlop, DCrispin, DBowden, TScanlan, CWard, ASchief, WDoores, KCrispin, MThe 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. |
| spellingShingle | Pritchard, L Spencer, D Royle, L Bonomelli, C Seabright, G Behrens, A Kulp, D Menis, S Krumm, S Dunlop, D Crispin, D Bowden, T Scanlan, C Ward, A Schief, W Doores, K Crispin, M Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies. |
| title | Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies. |
| title_full | Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies. |
| title_fullStr | Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies. |
| title_full_unstemmed | Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies. |
| title_short | Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies. |
| title_sort | glycan clustering stabilizes the mannose patch of hiv 1 and preserves vulnerability to broadly neutralizing antibodies |
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