Evidence map›Paper›PMID 28146569›Full record

ArticlePloS one2017

Human Gut-On-A-Chip Supports Polarized Infection of Coxsackie B1 Virus In Vitro.

Remi Villenave, Samantha Q Wales, Tiama Hamkins-Indik, Efstathia Papafragkou, James C Weaver, Thomas C Ferrante, Anthony Bahinski, Christopher A Elkins, Michael Kulka, Donald E Ingber

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
10.7field-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

92 citing papers in PubMed, 1 synthesis or guideline pooled it, 191 citations in OpenAlex.

  1. Advances in Engineering Human Tissue Models.Frontiers in bioengineering and biotechnology · 2020
    Pooled it
  2. Review
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  4. Review
  5. Review
  6. Article
  7. Review
  8. Gastrointestinal tract, its pathophysiology andWorld journal of gastroenterology · 2025
    Review
  9. Review
  10. Review
  11. Organs on chips: fundamentals, bioengineering and applications.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2025
    Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Microphysiological gut-on-chip enables extendedFrontiers in cellular and infection microbiology · 2025
    Article
  18. Review
  19. Intestinal organ chips for disease modelling and personalized medicine.Nature reviews. Gastroenterology & hepatology · 2024
    Review
  20. Review

32 more citing papers are in PubMed but not listed here.

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 4 institutions in 1 country.

Remi VillenaveWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, United States of America.
Samantha Q WalesMolecular Virology Team, Division of Molecular Biology, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, Maryland, United States of America.
Tiama Hamkins-IndikWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, United States of America.
Efstathia PapafragkouMolecular Virology Team, Division of Molecular Biology, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, Maryland, United States of America.
James C WeaverWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, United States of America.
Thomas C FerranteWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, United States of America.
Anthony BahinskiWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, United States of America.
Christopher A ElkinsMolecular Virology Team, Division of Molecular Biology, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, Maryland, United States of America.
Michael KulkaMolecular Virology Team, Division of Molecular Biology, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, Maryland, United States of America.
Donald E IngberWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, United States of America.
Harvard University · USCenter for Food Safety and Applied Nutrition · USBoston Children's Hospital · USUnited States Food and Drug Administration · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Analysis of enterovirus infection is difficult in animals because they express different virus receptors than humans, and static cell culture systems do not reproduce the physical complexity of the human intestinal epithelium. Here, using coxsackievirus B1 (CVB1) as a prototype enterovirus strain, we demonstrate that human enterovirus infection, replication and infectious virus production can be analyzed in vitro in a human Gut-on-a-Chip microfluidic device that supports culture of highly differentiated human villus intestinal epithelium under conditions of fluid flow and peristalsis-like motions. When CVB1 was introduced into the epithelium-lined intestinal lumen of the device, virions entered the epithelium, replicated inside the cells producing detectable cytopathic effects (CPEs), and both infectious virions and inflammatory cytokines were released in a polarized manner from the cell apex, as they could be detected in the effluent from the epithelial microchannel. When the virus was introduced via a basal route of infection (by inoculating virus into fluid flowing through a parallel lower 'vascular' channel separated from the epithelial channel by a porous membrane), significantly lower viral titers, decreased CPEs, and delayed caspase-3 activation were observed; however, cytokines continued to be secreted apically. The presence of continuous fluid flow through the epithelial lumen also resulted in production of a gradient of CPEs consistent with the flow direction. Thus, the human Gut-on-a-Chip may provide a suitable in vitro model for enteric virus infection and for investigating mechanisms of enterovirus pathogenesis.

Indexed as

Lab-On-A-Chip DevicesApoptosisCaco-2 CellsCaspasesCells, CulturedCoxsackievirus InfectionsCytokinesCytopathogenic Effect, ViralEnterovirus B, HumanHumansIntestinal MucosaViral Plaque AssayVirus ReplicationCaspasesCytokines

Identifiers

PMID28146569
PMCPMC5287454
OpenAlexW2585848172

What OpenQuestion holds

Textmetadata
LicenceCC0
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.