Evidence map›Paper›PMID 27162029›Full record

ArticleCell stem cell2016

Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3.

Jason Dang, Shashi Kant Tiwari, Gianluigi Lichinchi, Yue Qin, Veena S Patil, Alexey M Eroshkin, Tariq M Rana

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 429 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
429citing papers in PubMed, 2 pooled it
104.1field-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

429 citing papers in PubMed, 2 syntheses or guidelines pooled it, 718 citations in OpenAlex.

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369 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

7 authors at 2 institutions in 1 country.

Jason DangDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
Shashi Kant TiwariDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Gianluigi LichinchiDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Yue QinDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Veena S PatilDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Alexey M EroshkinBioinformatics core, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Tariq M RanaDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: trana@ucsd.edu.
University of California San Diego · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
Mechanisms of innate immunity against HIVR01AI043198 · NIAID · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI RANA, TARIQ M · 1998 to 2014
$4.7M
Modeling HIV/AIDS Associated Neurological Disorders with Human Pluripotent CellsDP1DA039562 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RANA, TARIQ M · 2015 to 2020
$3.9M
Regulation of HIV-1 Replication by Cellular IncRNAsR21AI125103 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RANA, TARIQ M · 2016 to 2017
$426k
NCI NIH HHS P30 CA030199NIAID NIH HHS R01 AI043198NIAID NIH HHS R21 AI125103NIDA NIH HHS DP1 DA039562
6 · The paper itself

Abstract

Emerging evidence from the current outbreak of Zika virus (ZIKV) indicates a strong causal link between Zika and microcephaly. To investigate how ZIKV infection leads to microcephaly, we used human embryonic stem cell-derived cerebral organoids to recapitulate early stage, first trimester fetal brain development. Here we show that a prototype strain of ZIKV, MR766, efficiently infects organoids and causes a decrease in overall organoid size that correlates with the kinetics of viral copy number. The innate immune receptor Toll-like-Receptor 3 (TLR3) was upregulated after ZIKV infection of human organoids and mouse neurospheres and TLR3 inhibition reduced the phenotypic effects of ZIKV infection. Pathway analysis of gene expression changes during TLR3 activation highlighted 41 genes also related to neuronal development, suggesting a mechanistic connection to disrupted neurogenesis. Together, therefore, our findings identify a link between ZIKV-mediated TLR3 activation, perturbed cell fate, and a reduction in organoid volume reminiscent of microcephaly.

Indexed as

Immunity, InnateAnimalsApoptosisCell DifferentiationCerebrumFetusHumansMiceNeural Stem CellsNeurogenesisOrganoidsRNAToll-Like Receptor 3Zika VirusZika Virus InfectionRNATLR3 protein, humanToll-Like Receptor 3microcephalyorganoidsToll-like receptorsZika virus

Identifiers

PMID27162029
PMCPMC5116380
OpenAlexW2346484133

What OpenQuestion holds

Textmetadata
LicenceTDM
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.