Evidence map›Paper›PMID 33093196›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Visualization of the HIV-1 Env glycan shield across scales.

Zachary T Berndsen, Srirupa Chakraborty, Xiaoning Wang, Christopher A Cottrell, Jonathan L Torres, Jolene K Diedrich, Cesar A López, John R Yates, Marit J van Gils, James C Paulson and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
7.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 92 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Zachary T BerndsenDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0003-4531-9907
Srirupa ChakrabortyTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545.
Xiaoning WangThe International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0003-0153-324X
Christopher A CottrellDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0002-3364-3083
Jonathan L TorresDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0003-0137-8497
Jolene K DiedrichDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037.
Cesar A LópezTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545.ORCID 0000-0003-4684-3364
John R YatesDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0001-5267-1672
Marit J van GilsDepartment of Medical Microbiology, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
James C PaulsonThe International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0003-4589-5322
Sandrasegaram GnanakaranTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545; gnana@lanl.gov andrew@scripps.edu.ORCID 0000-0002-9368-3044
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037; gnana@lanl.gov andrew@scripps.edu.ORCID 0000-0001-7153-3769
Scripps Research Institute · USLos Alamos National Laboratory · USUniversity of Amsterdam · NL

Funding

Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI SANTRA, SAMPA · 2012 to 2018
$204.7M
Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
Nonhuman primate studies for development of a prototype HIV vaccine that induces broadly neutralizing antibodiesUM1AI144371 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2019 to 2025
$190.4M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI MACCOSS, MICHAEL · 2012 to 2021
$20.7M
Glycan dependent epitopes of HIV broadly neutralizing antibodiesR01AI113867 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C, SCHIEF, WILLIAM R. · 2014 to 2018
$4.8M
Glycan dependent epitopes of HIV broadly neutralizing antibodiesR56AI113867 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C, SCHIEF, WILLIAM R. · 2020 to 2020
$887k
Broadening autologous Tier 2 anti-HIV neutralizing antibodiesF31AI131873 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI COTTRELL, CHRISTOPHER ANDREW · 2017 to 2020
$95k
NIAID NIH HHS F31 AI131873NIAID NIH HHS R01 AI113867NIAID NIH HHS R56 AI113867NIAID NIH HHS UM1 AI100645NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI144371NIAID NIH HHS UM1 AI144462NIGMS NIH HHS P41 GM103533
6 · The paper itself

Abstract

The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis. Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels. We found that dynamics lead to an extensive network of interglycan interactions that drive the formation of higher-order structure within the glycan shield. This structure defines diffuse boundaries between buried and exposed protein surface and creates a mapping of potentially immunogenic sites on Env. Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility. Importantly, this identified unforeseen changes in the glycan shield of Env obtained from expression in the same cell line used for vaccine production. Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.

Indexed as

Antibodies, NeutralizingAntibody FormationComputer SimulationCryoelectron Microscopyenv Gene Products, Human Immunodeficiency VirusEpitopesGlycosylationHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV SeropositivityHumansImmune EvasionMass SpectrometryModels, MolecularPolysaccharidesAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusEpitopesHIV AntibodiesHIV Envelope Protein gp120Polysaccharidescryo-EMglycoproteinHIV-1molecular modelingvaccine

Identifiers

PMID33093196
PMCPMC7668054
OpenAlexW3094127650

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.