Abstract
SummaryThe HIV-1 envelope glycoprotein trimer is covered by an array of N-linked glycans that shield it from immune surveillance. The high density of glycans on the trimer surface imposes steric constraints limiting the actions of glycan-processing enzymes, so that multiple under-processed structures remain on specific areas. These oligomannose glycans are recognized by broadly neutralizing antibodies (bNAbs) that are not thwarted by the glycan shield but, paradoxically, target it. Our site-specific glycosylation analysis of a soluble, recombinant trimer (BG505 SOSIP.664) maps the extremes of simplicity and diversity of glycan processing at individual sites and reveals a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, we identify examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens.
Highlights
The trimeric HIV type 1 (HIV-1) envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies produced by the immune system during infection and is, a focus of vaccine design
The HIV-1 envelope glycoprotein trimer is covered by an array of N-linked glycans that shield it from immune surveillance
The high density of glycans on the trimer surface imposes steric constraints limiting the actions of glycan-processing enzymes, so that multiple under-processed structures remain on specific areas
Summary
Behrens et al present detailed, quantitative, site-specific analyses of N-glycosylation sites of a soluble recombinant HIV-1 envelope glycoprotein trimer. The results highlight structural and antigenic details of the glycan shield that will be valuable for designing nextgeneration HIV-1 Env vaccines and understanding virus neutralization by broadly active antibodies. Highlights d Quantitative, site-specific N-glycan analysis of a soluble HIV-1 Env trimer d A map of the extremes of simplicity and diversity at individual glycan sites d The fine structure of the mannose patch area of the Env trimer d How individual glycan sites influence HIV-1 Env-pseudovirus neutralization.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
