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

TitleGlycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies.
Publication TypeJournal Article
Year of Publication2015
AuthorsPritchard LK, Spencer DIR, Royle L, Bonomelli C, Seabright GE, Behrens A-J, Kulp DW, Menis S, Krumm SA, Dunlop CD, Crispin DJ, Bowden TA, Scanlan CN, Ward AB, Schief WR, Doores KJ, Crispin M
JournalNat Commun
Volume6
Pagination7479
Date Published06/24/2015
ISSN2041-1723
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.

DOI10.1038/ncomms8479
Alternate JournalNat Commun
PubMed ID26105115
PubMed Central IDPMC4500839
Grant List1UM1AI100663 / AI / NIAID NIH HHS / United States
MR/K024426/1 / / Medical Research Council / United Kingdom
MR/L009528/1 / / Wellcome Trust / United Kingdom
P01AI081625 / AI / NIAID NIH HHS / United States
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