Evidence map›Paper›PMID 36154279›Full record

ArticleMicrobiology spectrum2022

Enterovirus D68 Infection in Human Primary Airway and Brain Organoids: No Additional Role for Heparan Sulfate Binding for Neurotropism.

Adithya Sridhar, Josse A Depla, Lance A Mulder, Eveliina Karelehto, Lieke Brouwer, Leonie Kruiswijk, Renata Vieira de Sá, Adam Meijer, Melvin M Evers, Frank J M van Kuppeveld and 2 more

Open access · goldAbstract read
In one paragraph

Article in Microbiology spectrum, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 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 5 institutions in 1 country.

Adithya Sridhar *Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Department of Medical Microbiology, OrganoVIR Labs, Amsterdam, The Netherlands.ORCID 0000-0003-2986-4884
Josse A Depla *Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Department of Medical Microbiology, OrganoVIR Labs, Amsterdam, The Netherlands.
Lance A MulderAmsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Department of Medical Microbiology, OrganoVIR Labs, Amsterdam, The Netherlands.
Eveliina KarelehtoAmsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Department of Medical Microbiology, OrganoVIR Labs, Amsterdam, The Netherlands.
Lieke BrouwerAmsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Department of Medical Microbiology, OrganoVIR Labs, Amsterdam, The Netherlands.
Leonie KruiswijkAmsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Department of Medical Microbiology, OrganoVIR Labs, Amsterdam, The Netherlands.
Renata Vieira de SáuniQure Biopharma B.V., Amsterdam, The Netherlands.
Adam MeijerNational Institute for Public Health and Environment, Centre for Infectious Diseases Research and Laboratory Surveillance, Bilthoven, The Netherlands.
Melvin M EversuniQure Biopharma B.V., Amsterdam, The Netherlands.
Frank J M van KuppeveldVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht Universitygrid.5477.1, Utrecht, The Netherlands.
Dasja Pajkrt *Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Department of Medical Microbiology, OrganoVIR Labs, Amsterdam, The Netherlands.
Katja C Wolthers *Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Department of Medical Microbiology, OrganoVIR Labs, Amsterdam, The Netherlands.
Emma Kinderziekenhuis · NLAmsterdam University Medical Centers · NLUniQure (Netherlands) · NLNational Institute for Public Health and the Environment · NLUtrecht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Enterovirus D68 (EV-D68) is an RNA virus that can cause outbreaks of acute flaccid paralysis (AFP), a polio-like disease. Before 2010, EV-D68 was a rare pathogen associated with mild respiratory symptoms, but the recent EV-D68 related increase in severe respiratory illness and outbreaks of AFP is not yet understood. An explanation for the rise in severe disease is that it may be due to changes in the viral genome resulting in neurotropism. In this regard, in addition to sialic acid, binding to heparan sulfate proteoglycans (HSPGs) has been identified as a feature for viral entry of some EV-D68 strains in cell lines. Studies in human primary organotypic cultures that recapitulate human physiology will address the relevance of these HSPG-binding mutations for EV-D68 infection in vivo. Therefore, in this work, we studied the replication and neurotropism of previously determined sialic acid-dependent and HSPG-dependent strains using primary human airway epithelial (HAE) cultures and induced human pluripotent stem cell (iPSC)-derived brain organoids. All three strains (B2/2042, B2/947, and A1/1348) used in this study infected HAE cultures and human brain organoids (shown for the first time). Receptor-blocking experiments in both cultures confirm that B2/2042 infection is solely dependent on sialic acid, while B2/947 and A1/1348 (HSPG to a lesser extent) binds to sialic acid and HSPG for cell entry. Our data suggest that HSPG-binding can be used by EV-D68 for entry in human physiological models but offers no advantage for EV-D68 infection of brain cells.

Indexed as

Enterovirus D, HumanEnterovirus InfectionsBrainChildChild, PreschoolHeparan Sulfate ProteoglycansHumansN-Acetylneuraminic AcidOrganoidsHeparan Sulfate ProteoglycansN-Acetylneuraminic Acidcerebral organoidsenterovirusenterovirus D68human airway epithelial cultures (HAE)neurotropismreceptors

Identifiers

PMID36154279
PMCPMC9603061
OpenAlexW4297217722

What OpenQuestion holds

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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 OpenQuestion graph.