|Title||Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Pritchard 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|
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.
|Alternate Journal||Nat Commun|
|PubMed Central ID||PMC4500839|
|Grant List||1UM1AI100663 / 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
Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies.