Evidence map›Paper›PMID 30075025›Full record

ArticlePLoS pathogens2018

A VP1 mutation acquired during an enterovirus 71 disseminated infection confers heparan sulfate binding ability and modulates ex vivo tropism.

Eirini D Tseligka, Komla Sobo, Luc Stoppini, Valeria Cagno, Fabien Abdul, Isabelle Piuz, Pascal Meylan, Song Huang, Samuel Constant, Caroline Tapparel

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

54 citing papers in PubMed, 70 citations in OpenAlex.

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  4. Serial passagingFrontiers in cellular and infection microbiology · 2026
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  8. Pathogens that infect mammalian cells via sulfonated glycosaminoglycans.Frontiers in cellular and infection microbiology · 2025
    Review
  9. Article
  10. Review
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  14. Article
  15. Antiviral properties of trans-δ-viniferin derivatives against enveloped viruses.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023
    Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Positive-strand RNA viruses-a Keystone Symposia report.Annals of the New York Academy of Sciences · 2023
    Article
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

10 authors at 3 institutions in 1 country.

Eirini D TseligkaDepartment of Microbiology and Molecular Medicine, University of Geneva Medical School, Geneva, Switzerland.
Komla SoboDepartment of Microbiology and Molecular Medicine, University of Geneva Medical School, Geneva, Switzerland.
Luc StoppiniTissue Engineering Laboratory, HES-SO/University of Applied Sciences, Geneva, Western Switzerland.
Valeria CagnoDepartment of Microbiology and Molecular Medicine, University of Geneva Medical School, Geneva, Switzerland.ORCID 0000-0002-5597-334X
Fabien AbdulDepartment of Microbiology and Molecular Medicine, University of Geneva Medical School, Geneva, Switzerland.
Isabelle PiuzDepartment of Microbiology and Molecular Medicine, University of Geneva Medical School, Geneva, Switzerland.
Pascal MeylanInstitute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Song HuangEpithelix Sàrl, Geneva, Switzerland.
Samuel ConstantEpithelix Sàrl, Geneva, Switzerland.
Caroline TapparelDepartment of Microbiology and Molecular Medicine, University of Geneva Medical School, Geneva, Switzerland.ORCID 0000-0002-0411-6567
University of Geneva · CHHES-SO University of Applied Sciences and Arts Western Switzerland · CHUniversity Hospital of Lausanne · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Enterovirus 71 (EV71) causes hand, foot and mouth disease, a mild and self-limited illness that is sometimes associated with severe neurological complications. EV71 neurotropic determinants remain ill-defined to date. We previously identified a mutation in the VP1 capsid protein (L97R) that was acquired over the course of a disseminated infection in an immunocompromised host. The mutation was absent in the respiratory tract but was present in the gut (as a mixed population) and in blood and cerebrospinal fluid (as a dominant species). In this study, we demonstrated that this mutation does not alter the dependence of EV71 on the human scavenger receptor class B2 (SCARB2), while it enables the virus to bind to the heparan sulfate (HS) attachment receptor and modifies viral tropism in cell lines and in respiratory, intestinal and neural tissues. Variants with VP197L or VP197R were able to replicate to high levels in intestinal and neural tissues and, to a lesser extent, in respiratory tissues, but their preferred entry site (from the luminal or basal tissue side) differed in respiratory and intestinal tissues and correlated with HS expression levels. These data account for the viral populations sequenced from the patient's respiratory and intestinal samples and suggest that improved dissemination, resulting from an acquired ability to bind HS, rather than specific neurotropism determinants, enabled the virus to reach and infect the central nervous system. Finally, we showed that iota-carrageenan, a highly sulfated polysaccharide, efficiently blocks the replication of HS-dependent variants in cells and 2D neural cultures. Overall, the results of this study emphasize the importance of HS binding in EV71 pathogenesis and open new avenues for the development of antiviral molecules that may prevent this virus's dissemination.

Indexed as

AnimalsCapsid ProteinsEnterovirus A, HumanHand, Foot and Mouth DiseaseHeparan SulfateHumansLysosomal Membrane ProteinsMiceMutationReceptors, ScavengerViral TropismVirus ReplicationCapsid ProteinsHeparan SulfateLysosomal Membrane ProteinsReceptors, ScavengerSCARB2 protein, human

Identifiers

PMID30075025
PMCPMC6093697
OpenAlexW2885989360

What OpenQuestion holds

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LicenceCC BY
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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.