Integrity of Glycosylation Processing of a Glycan-Depleted Trimeric HIV-1 Immunogen Targeting Key B-Cell Lineages.

TitleIntegrity of Glycosylation Processing of a Glycan-Depleted Trimeric HIV-1 Immunogen Targeting Key B-Cell Lineages.
Publication TypeJournal Article
Year of Publication2018
AuthorsBehrens A-J, Kumar A, Medina-Ramírez M, Cupo A, Marshall K, Portillo VMCruz, Harvey DJ, Ozorowski G, Zitzmann N, Wilson IA, Ward AB, Struwe WB, Moore JP, Sanders RW, Crispin M
JournalJ Proteome Res
Volume17
Issue3
Pagination987-999
Date Published03/02/2018
ISSN1535-3907
Abstract

Broadly neutralizing antibodies (bNAbs) that target the trimeric HIV-1 envelope glycoprotein spike (Env) are tools that can guide the design of recombinant Env proteins intended to engage the predicted human germline precursors of bNAbs (gl-bNAbs). The protein components of gl-bNAb epitopes are often masked by glycans, while mature bNAbs can evolve to accommodate or bypass these shielding glycans. The design of germline-targeting Env immunogens therefore includes the targeted deletion of specific glycan sites. However, the processing of glycans on Env trimers can be influenced by the density with which they are packed together, a highly relevant point given the essential contributions under-processed glycans make to multiple bNAb epitopes. We sought to determine the impact of the removal of 15 potential N-glycan sites (5 per protomer) from the germline-targeting soluble trimer, BG505 SOSIP.v4.1-GT1, using quantitative, site-specific N-glycan mass spectrometry analysis. We find that, compared with SOSIP.664, there was little overall change in the glycan profile but only subtle increases in the extent of processing at sites immediately adjacent to where glycans had been deleted. We conclude that multiple glycans can be deleted from BG505 SOSIP trimers without perturbing the overall integrity of the glycan shield.

DOI10.1021/acs.jproteome.7b00639
Alternate JournalJ. Proteome Res.
PubMed ID29420040
PubMed Central IDPMC5846105
Grant ListP01 AI110657 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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