Evidence map›Paper›PMID 34669426›Full record

ArticleJournal of virology2022

The Glycan Hole Area of HIV-1 Envelope Trimers Contributes Prominently to the Induction of Autologous Neutralization.

Anna Schorcht, Christopher A Cottrell, Pavel Pugach, Rajesh P Ringe, Alvin X Han, Joel D Allen, Tom L G M van den Kerkhof, Gemma E Seabright, Edith E Schermer, Thomas J Ketas and 15 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.3field-weighted citation impact, top 18% 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

22 citing papers in PubMed, 17 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

25 authors at 6 institutions in 3 countries.

Anna SchorchtDepartment of Medical Microbiology and Infection Prevention, Amsterdam Infection & Immunity Institute (AI&AII), Amsterdam UMC, Location Meibergdreef, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0003-1548-790X
Christopher A CottrellDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Pavel PugachDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA.
Rajesh P RingeDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA.
Alvin X HanLaboratory of Applied Evolutionary Biology, Department of Medical Microbiology and Infection Prevention, Amsterdam Infection & Immunity Institute (AI&AII), Amsterdam UMC, Location Meibergdreef, University of Amsterdam, Amsterdam, The Netherlands.
Joel D AllenCentre for Biological Sciences and Institute for Life Sciences, University of Southamptongrid.5491.9, Southampton, England, United Kingdom.
Tom L G M van den KerkhofDepartment of Medical Microbiology and Infection Prevention, Amsterdam Infection & Immunity Institute (AI&AII), Amsterdam UMC, Location Meibergdreef, University of Amsterdam, Amsterdam, The Netherlands.
Gemma E SeabrightCentre for Biological Sciences and Institute for Life Sciences, University of Southamptongrid.5491.9, Southampton, England, United Kingdom.
Edith E SchermerDepartment of Medical Microbiology and Infection Prevention, Amsterdam Infection & Immunity Institute (AI&AII), Amsterdam UMC, Location Meibergdreef, University of Amsterdam, Amsterdam, The Netherlands.
Thomas J KetasDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA.
Judith A BurgerDepartment of Medical Microbiology and Infection Prevention, Amsterdam Infection & Immunity Institute (AI&AII), Amsterdam UMC, Location Meibergdreef, University of Amsterdam, Amsterdam, The Netherlands.
Jelle van SchootenDepartment of Medical Microbiology and Infection Prevention, Amsterdam Infection & Immunity Institute (AI&AII), Amsterdam UMC, Location Meibergdreef, University of Amsterdam, Amsterdam, The Netherlands.
Celia C LaBrancheDepartment of Surgery, Duke Universitygrid.26009.3d Medical Center, Durham, North Carolina, USA.ORCID 0000-0002-6653-6655
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.ORCID 0000-0002-9695-8138
Natalia de ValDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Daniel L V BaderDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Hanneke SchuitemakerDepartment of Experimental Immunology, Amsterdam Infection & Immunity Institute (AI&AII), Amsterdam UMC, Location Meibergdreef, University of Amsterdam, Amsterdam, The Netherlands.
Colin A RussellLaboratory of Applied Evolutionary Biology, Department of Medical Microbiology and Infection Prevention, Amsterdam Infection & Immunity Institute (AI&AII), Amsterdam UMC, Location Meibergdreef, University of Amsterdam, Amsterdam, The Netherlands.
David C MontefioriDepartment of Surgery, Duke Universitygrid.26009.3d Medical Center, Durham, North Carolina, USA.
Marit J van GilsDepartment of Medical Microbiology and Infection Prevention, Amsterdam Infection & Immunity Institute (AI&AII), Amsterdam UMC, Location Meibergdreef, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0003-3422-8161
Max CrispinCentre for Biological Sciences and Institute for Life Sciences, University of Southamptongrid.5491.9, Southampton, England, United Kingdom.
P J KlasseDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.ORCID 0000-0001-7153-3769
John P MooreDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA.ORCID 0000-0002-9902-6096
Rogier W SandersDepartment of Medical Microbiology and Infection Prevention, Amsterdam Infection & Immunity Institute (AI&AII), Amsterdam UMC, Location Meibergdreef, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0001-5598-1780
Cornell University · USUniversity of Amsterdam · NLAmsterdam University Medical Centers · NLScripps Research Institute · USUniversity of Southampton · GBDuke Medical Center · US

Funding

Structural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4M
Neutralization of Primate Immunodeficiency VirusesR01AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI JOHN P MOORE · 1994 to 2026
$4.3M
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 P01 AI110657NIAID NIH HHS R01 AI036082
6 · The paper itself

Abstract

The human immunodeficiency virus type 1 (HIV-1) trimeric envelope glycoprotein (Env) is heavily glycosylated, creating a dense glycan shield that protects the underlying peptidic surface from antibody recognition. The absence of conserved glycans, due to missing potential N-linked glycosylation sites (PNGS), can result in strain-specific, autologous neutralizing antibody (NAb) responses. Here, we sought to gain a deeper understanding of the autologous neutralization by introducing holes in the otherwise dense glycan shields of the AMC011 and AMC016 SOSIP trimers. Specifically, when we knocked out the N130 and N289 glycans, which are absent from the well-characterized B41 SOSIP trimer, we observed stronger autologous NAb responses. We also analyzed the highly variable NAb responses induced in rabbits by diverse SOSIP trimers from subtypes A, B, and C. Statistical analysis, using linear regression, revealed that the cumulative area exposed on a trimer by glycan holes correlates with the magnitude of the autologous NAb response.

Indexed as

Protein MultimerizationAIDS VaccinesAmino AcidsAnimalsAntibodies, NeutralizingAntibody FormationAntigens, Viralenv Gene Products, Human Immunodeficiency VirusGlycosylationHIV-1HIV AntibodiesHIV InfectionsHost-Pathogen InteractionsHumansImmunizationModels, MolecularAIDS VaccinesAmino AcidsAntibodies, NeutralizingAntigens, Viralenv Gene Products, Human Immunodeficiency VirusHIV AntibodiesPolysaccharidesautologous neutralizationEnv trimerglycan shieldHIV-1immunizationSOSIPvaccine

Identifiers

PMID34669426
PMCPMC8754230
OpenAlexW3207758379

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.