Evidence map›Paper›PMID 38193662›Full record

ArticlemBio2024

SARS-CoV-2 spike glycosylation affects function and neutralization sensitivity.

Fengwen Zhang, Fabian Schmidt, Frauke Muecksch, Zijun Wang, Anna Gazumyan, Michel C Nussenzweig, Christian Gaebler, Marina Caskey, Theodora Hatziioannou, Paul D Bieniasz

Open access · goldAbstract read
In one paragraph

Article in mBio, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
12.4field-weighted citation impact, top 1% 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

34 citing papers in PubMed, 33 citations in OpenAlex.

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  6. Constrained evolutionary funnels shape viral immune escape.Proceedings of the National Academy of Sciences of the United States of America · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Fengwen ZhangLaboratory of Retrovirology, The Rockefeller University, New York, New York, USA.
Fabian SchmidtLaboratory of Retrovirology, The Rockefeller University, New York, New York, USA.
Frauke MueckschLaboratory of Retrovirology, The Rockefeller University, New York, New York, USA.
Zijun WangLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
Anna GazumyanLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
Michel C NussenzweigLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.ORCID 0000-0003-0592-8564
Christian GaeblerLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
Marina CaskeyLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
Theodora HatziioannouLaboratory of Retrovirology, The Rockefeller University, New York, New York, USA.ORCID 0000-0002-7889-0766
Paul D BieniaszLaboratory of Retrovirology, The Rockefeller University, New York, New York, USA.ORCID 0000-0002-2368-3719
Rockefeller University · USHoward Hughes Medical Institute · US

Funding

The longevity and nature of the anti-SARS-CoV-2 cellular and humoral immune responsesP01AI165075 · NIAID · ROCKEFELLER UNIVERSITY · PI BIENIASZ, PAUL D., BJORKMAN, PAMELA J · 2022 to 2023
$10.7M
Overcoming Host Restriction Factors to Develop Better Animal Models for HIV/AIDS.R01AI078788 · NIAID · ROCKEFELLER UNIVERSITY · PI HATZIIOANNOU, THEODORA · 2008 to 2021
$9.3M
Discovery and Mechanism of Antiretroviral FactorsR37AI064003 · NIAID · ROCKEFELLER UNIVERSITY · PI BIENIASZ, PAUL D. · 2011 to 2020
$4.9M
Host protein targets of HIV-1 Vpr in gene expression, cell cycle and innate immunityR01AI157809 · NIAID · ROCKEFELLER UNIVERSITY · PI BIENIASZ, PAUL D. · 2020 to 2024
$2.1M
NIAID NIH HHS P01 AI165075NIAID NIH HHS R01 AI078788NIAID NIH HHS R01 AI157809NIAID NIH HHS R37 AI064003
6 · The paper itself

Abstract

The glycosylation of viral envelope proteins can play important roles in virus biology and immune evasion. The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) includes 22 N-linked glycosylation sequons and 17 O-linked glycosites. We investigated the effect of individual glycosylation sites on SARS-CoV-2 S function in pseudotyped virus infection assays and on sensitivity to monoclonal and polyclonal neutralizing antibodies. In most cases, the removal of individual glycosylation sites decreased the infectiousness of the pseudotyped virus. For glycosylation mutants in the N-terminal domain and the receptor-binding domain (RBD), reduction in pseudotype infectivity was predicted by a commensurate reduction in the level of virion-incorporated S protein and reduced S trafficking to the cell surface. Notably, the presence of a glycan at position N343 within the RBD had diverse effects on neutralization by RBD-specific monoclonal antibodies cloned from convalescent individuals. The N343 glycan reduced the overall sensitivity to polyclonal antibodies in plasma from COVID-19 convalescent individuals, suggesting a role for SARS-CoV-2 S glycosylation in immune evasion. However, vaccination of convalescent individuals produced neutralizing activity that was resilient to the inhibitory effect of the N343 glycan.IMPORTANCEThe attachment of glycans to the spike proteins of viruses during their synthesis and movement through the secretory pathway can affect their properties. This study shows that the glycans attached to the severe acute respiratory syndrome coronavirus-2 spike protein enable its movement to the cell surface and incorporation into virus particles. Certain glycans, including one that is attached to asparagine 343 in the receptor-binding domain of the spike protein, can also affect virus neutralization by antibodies. This glycan can increase or decrease sensitivity to individual antibodies, likely through direct effects on antibody epitopes and modulation of spike conformation. However, the overall effect of the glycan in the context of the polyclonal mixture of antibodies in convalescent serum is to reduce neutralization sensitivity. Overall, this study highlights the complex effects of glycosylation on spike protein function and immune evasion.

Indexed as

COVID-19SARS-CoV-2Antibodies, NeutralizingAntibodies, ViralCOVID-19 SerotherapyGlycosylationHumansNeutralization TestsPolysaccharidesSpike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralPolysaccharidesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2antibody functionglycosylationneutralizationSARS-CoV-2

Identifiers

PMID38193662
PMCPMC10865855
OpenAlexW4390777542

What OpenQuestion holds

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LicenceCC BY
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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.