Evidence map›Paper›PMID 31671153›Full record

ArticlePLoS pathogens2019

Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape.

Abimbola O Kolawole, Carmen Mirabelli, David R Hill, Sophia A Svoboda, Andrew B Janowski, Karla D Passalacqua, Benancio N Rodriguez, Michael K Dame, Pamela Freiden, Ryan P Berger and 8 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
8.5field-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

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Microorganisms · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Neonatal Fc receptor is a functional receptor for classical human astrovirus.Genes to cells : devoted to molecular & cellular mechanisms · 2024
    Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review

9 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

18 authors at 5 institutions in 3 countries.

Abimbola O KolawoleDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
Carmen MirabelliDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
David R HillDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-1626-6079
Sophia A SvobodaDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-1850-8166
Andrew B JanowskiDepartment of Pediatrics, Washington University, St. Louis, Missouri, United States of America.ORCID 0000-0003-4382-1194
Karla D PassalacquaDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
Benancio N RodriguezDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
Michael K DameDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0003-3760-1654
Pamela FreidenSt. Jude Children's Hospital, Memphis, Tennessee, United States of America.
Ryan P BergerDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
Diem-Lan VuEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain.
Myra HosmilloDivision of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.ORCID 0000-0002-3514-7681
Mary X D O'RiordanDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
Stacey Schultz-CherrySt. Jude Children's Hospital, Memphis, Tennessee, United States of America.
Susana GuixEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain.ORCID 0000-0002-1588-3198
Jason R SpenceDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
David WangDepartments of Molecular Microbiology, and Pathology and Immunology, Washington University, St. Louis, Missouri, United States of America.
Christiane E WobusDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-5286-0924
University of Michigan · USSt. Jude Children's Research Hospital · USUniversitat de Barcelona · ESWashington University in St. Louis · USUniversity of Cambridge · GB

Funding

Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
Intestinal Stem Cell Consortium Coordinating CenterU01DK085532 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2009 to 2018
$6.5M
Stem Cell Differentiation CoreU19AI116482 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SPENCE, JASON, TAKAYAMA, SHUICHI · 2015 to 2019
$6.4M
Niche support of human intestinal stem cellsU01DK103141 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SPENCE, JASON · 2014 to 2023
$3.9M
Limited Competition for the Continuation of the Intestinal Stem Cell Consortium Coordinating CenterU24DK085532 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2019 to 2023
$2.3M
CHARACTERIZATION OF ASTROVIRUS VA1, A NOVEL NEUROTROPIC VIRUSK08AI132745 · NIAID · WASHINGTON UNIVERSITY · PI JANOWSKI, ANDREW BOK SENG · 2018 to 2022
$809k
Do they or don't they: astrovirus-induced diarrheaR21AI135254 · NIAID · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI SCHULTZ-CHERRY, STACEY L · 2018 to 2019
$561k
Human astrovirus infection of human intestinal enteroidsR21AI141835 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WOBUS, CHRISTIANE · 2019 to 2020
$448k
PROPAGATION OF THE EMERGING ENCEPHALITIC VIRUS ASTROVIRUS VA1R21NS101371 · NINDS · WASHINGTON UNIVERSITY · PI WANG, DAVID · 2017 to 2018
$419k
NCATS NIH HHS UL1 TR000433NIAID NIH HHS K08 AI132745NIAID NIH HHS R21 AI135254NIAID NIH HHS R21 AI141835NIAID NIH HHS U19 AI116482NIDDK NIH HHS P30 DK034933NIDDK NIH HHS U01 DK085532NIDDK NIH HHS U01 DK103141NIDDK NIH HHS U24 DK085532NINDS NIH HHS R21 NS101371Wellcome TrustWellcome Trust 207498/Z/17/Z
6 · The paper itself

Abstract

Human astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type and VA-type have been reported in humans. One limitation towards a better understanding of these viruses has been the lack of a physiologically relevant cell culture model that supports growth of all clades of HAstV. Herein, we demonstrate infection of HAstV strains belonging to all three clades in epithelium-only human intestinal enteroids (HIE) isolated from biopsy-derived intestinal crypts. A detailed investigation of infection of VA1, a member of the non-canonical HAstV-VA/HMO clade, showed robust replication in HIE derived from different patients and from different intestinal regions independent of the cellular differentiation status. Flow cytometry and immunofluorescence analysis revealed that VA1 infects several cell types, including intestinal progenitor cells and mature enterocytes, in HIE cultures. RNA profiling of VA1-infected HIE uncovered that the host response to infection is dominated by interferon (IFN)-mediated innate immune responses. A comparison of the antiviral host response in non-transformed HIE and transformed human colon carcinoma Caco-2 cells highlighted significant differences between these cells, including an increased magnitude of the response in HIE. Additional studies confirmed the sensitivity of VA1 to exogenous IFNs, and indicated that the endogenous IFN response of HIE to curtail the growth of strains from all three clades. Genotypic variation in the permissiveness of different HIE lines to HAstV could be overcome by pharmacologic inhibition of JAK/STAT signaling. Collectively, our data identify HIE as a universal infection model for HAstV and an improved model of the intestinal epithelium to investigate enteric virus-host interactions.

Indexed as

AnimalsAstroviridae InfectionsCaco-2 CellsCell LineChlorocebus aethiopsEnterocytesGastroenteritisHumansImmunity, InnateInterferonsIntestinal MucosaIntestine, SmallMamastrovirusVero CellsViral TropismInterferons

Identifiers

PMID31671153
PMCPMC6957189
OpenAlexW2986542070

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.