Evidence map›Paper›PMID 30327438›Full record

ArticlemBio2018

Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells.

David M Brown, Alison M Hixon, Lauren M Oldfield, Yun Zhang, Mark Novotny, Wei Wang, Suman R Das, Reed S Shabman, Kenneth L Tyler, Richard H Scheuermann

Open access · goldAbstract read
In one paragraph

Article in mBio, 2018. 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
10.4field-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

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

David M BrownJ. Craig Venter Institute, Rockville, Maryland, USA.
Alison M HixonNeuroscience Program and Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, Colorado, USA.
Lauren M OldfieldJ. Craig Venter Institute, Rockville, Maryland, USA.
Yun ZhangJ. Craig Venter Institute, La Jolla, California, USA.
Mark NovotnyJ. Craig Venter Institute, La Jolla, California, USA.
Wei WangJ. Craig Venter Institute, Rockville, Maryland, USA.
Suman R DasJ. Craig Venter Institute, Rockville, Maryland, USA.
Reed S ShabmanJ. Craig Venter Institute, Rockville, Maryland, USA.
Kenneth L TylerDepartment of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Richard H ScheuermannJ. Craig Venter Institute, La Jolla, California, USA RScheuermann@jcvi.org.ORCID 0000-0003-1355-892X
J. Craig Venter Institute · USDenver VA Medical Center · USUniversity of Colorado Denver · US

Funding

Medical Scientist Training ProgramT32GM008497 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI WILSON, CARA C. · 1993 to 2022
$15.2M
Molecular Pathogenesis of Infectious DiseasesT32AI052066 · NIAID · UNIVERSITY OF COLORADO DENVER · PI VAN DYK, LINDA F. · 2002 to 2022
$2.3M
EV-D68-induced CNS disease: pathogenic mechanisms and identification of therapeutic targets.R01NS101208 · NINDS · UNIVERSITY OF COLORADO DENVER · PI TYLER, KENNETH L. · 2018 to 2021
$1.5M
EV-D68-induced CNS disease: pathogenic mechanisms and identification of therapeutic targets.R56NS101208 · NINDS · UNIVERSITY OF COLORADO DENVER · PI TYLER, KENNETH L. · 2017 to 2017
$340k
NIAID NIH HHS HHSN272201200005CNIAID NIH HHS HHSN272201400028CNIAID NIH HHS T32 AI052066NIGMS NIH HHS T32 GM008497NINDS NIH HHS R01 NS101208NINDS NIH HHS R56 NS101208
6 · The paper itself

Abstract

Enterovirus D68 (EV-D68) has historically been associated with respiratory illnesses. However, in the summers of 2014 and 2016, EV-D68 outbreaks coincided with a spike in polio-like acute flaccid myelitis/paralysis (AFM/AFP) cases. This raised concerns that EV-D68 could be the causative agent of AFM during these recent outbreaks. To assess the potential neurotropism of EV-D68, we utilized the neuroblastoma-derived neuronal cell line SH-SY5Y as a cell culture model to determine if differential infection is observed for different EV-D68 strains. In contrast to HeLa and A549 cells, which support viral infection of all EV-D68 strains tested, SH-SY5Y cells only supported infection by a subset of contemporary EV-D68 strains, including isolates from the 2014 outbreak. Viral replication and infectivity in SH-SY5Y were assessed using multiple assays: virus production, cytopathic effects, cellular ATP release, and VP1 capsid protein production. Similar differential neurotropism was also observed in differentiated SH-SY5Y cells, primary human neuron cultures, and a mouse paralysis model. Using the SH-SY5Y cell culture model, we determined that barriers to viral binding and entry were at least partly responsible for the differential infectivity phenotype. Transfection of genomic RNA into SH-SY5Y generated virions for all EV-D68 isolates, but only a single round of replication was observed from strains that could not directly infect SH-SY5Y. In addition to supporting virus replication and other functional studies, this cell culture model may help identify the signatures of virulence to confirm epidemiological associations between EV-D68 strains and AFM and allow for the rapid identification and characterization of emerging neurotropic strains.

Indexed as

Viral TropismVirus InternalizationVirus ReplicationA549 CellsAnimalsCell Culture TechniquesCell LineCentral Nervous System Viral DiseasesEnterovirus D, HumanEnterovirus InfectionsFemaleHeLa CellsHost Microbial InteractionsHumansMiceMyelitisenterovirusEV-D68myelitisneurotropismneurovirologySH-SY5Y

Identifiers

PMID30327438
PMCPMC6191546
OpenAlexW2897250439

What OpenQuestion holds

Textmetadata
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.