Evidence map›Paper›PMID 27524440›Full record

ArticleCell stem cell2016

Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal Neural Stem Cells to Inhibit Neurogenesis and Induce Autophagy.

Qiming Liang, Zhifei Luo, Jianxiong Zeng, Weiqiang Chen, Suan-Sin Foo, Shin-Ae Lee, Jianning Ge, Su Wang, Steven A Goldman, Berislav V Zlokovic and 2 more

Open access · bronzeAbstract 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 333 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
333citing papers in PubMed, 1 pooled it
57.5field-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

333 citing papers in PubMed, 1 synthesis or guideline pooled it, 552 citations in OpenAlex.

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273 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

12 authors at 2 institutions in 3 countries.

Qiming LiangDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address: liangqiming@shsmu.edu.cn.
Zhifei LuoDepartment of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Jianxiong ZengDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Weiqiang ChenDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Suan-Sin FooDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Shin-Ae LeeDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Jianning GeDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Su WangCenter for Translational Neuromedicine, University of Rochester, Rochester, NY 14642, USA; Department of Neurology, University of Rochester, Rochester, NY 14642, USA; Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark.
Steven A GoldmanCenter for Translational Neuromedicine, University of Rochester, Rochester, NY 14642, USA; Department of Neurology, University of Rochester, Rochester, NY 14642, USA; Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark.
Berislav V ZlokovicDepartment of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Zhen ZhaoDepartment of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: zzhao@usc.edu.
Jae U JungDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: jaeujung@med.usc.edu.
University of Southern California · USUniversity of Copenhagen · DK

Funding

VASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ARANDA, MARIA P. · 1985 to 2019
$41.0M
Roles of the K3 and K5 in KSHV Persistence and PathogenesisP01CA180779 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JUNG, JAE U · 2013 to 2017
$7.3M
Molecular Basis of KSHV oncogenesisR35CA200422 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JUNG, JAE U · 2016 to 2022
$6.1M
Role of viral BCI-2 mediated anti-apoptosis and-autophagyR01AI073099 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JUNG, JAE U · 2007 to 2017
$4.3M
KSHV Epigenetic RegulationR01DE023926 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JUNG, JAE U · 2013 to 2024
$4.2M
Activated protein C system in stroke modelsR01NS090904 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZLOKOVIC, BERISLAV V · 2014 to 2018
$3.2M
A Humanized Mouse Model of Astrocytic Pathology in SchizophreniaR01MH099578 · NIMH · UNIVERSITY OF ROCHESTER · PI GOLDMAN, STEVEN ALAN, NEDERGAARD, MAIKEN · 2013 to 2017
$2.8M
TRIM9-mediated anti-viral immune pathwayR01AI116585 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI OU, J.-H. JAMES · 2015 to 2019
$2.3M
An iPSC based humanized mouse model of dysmyelination in schizophreniaR01MH104701 · NIMH · UNIVERSITY OF ROCHESTER · PI GOLDMAN, STEVEN ALAN · 2014 to 2018
$2.1M
When Autophagy Meets PhagocytosisR01HL110609 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JUNG, JAE U · 2011 to 2015
$2.0M
Molecular Regulation of Human Glial Progenitor Cell-Based RemyelinationR01NS075345 · NINDS · UNIVERSITY OF ROCHESTER · PI GOLDMAN, STEVEN ALAN · 2011 to 2015
$1.7M
NCI NIH HHS P01 CA180779NCI NIH HHS R35 CA200422NHLBI NIH HHS R01 HL110609NIAID NIH HHS R01 AI073099NIAID NIH HHS R01 AI116585NIA NIH HHS P50 AG005142NIDCR NIH HHS R01 DE023926NIMH NIH HHS R01 MH099578NIMH NIH HHS R01 MH104701NINDS NIH HHS R01 NS075345NINDS NIH HHS R01 NS090904
6 · The paper itself

Abstract

The current widespread outbreak of Zika virus (ZIKV) infection has been linked to severe clinical birth defects, particularly microcephaly, warranting urgent study of the molecular mechanisms underlying ZIKV pathogenesis. Akt-mTOR signaling is one of the key cellular pathways essential for brain development and autophagy regulation. Here, we show that ZIKV infection of human fetal neural stem cells (fNSCs) causes inhibition of the Akt-mTOR pathway, leading to defective neurogenesis and aberrant activation of autophagy. By screening the three structural proteins and seven nonstructural proteins present in ZIKV, we found that two, NS4A and NS4B, cooperatively suppress the Akt-mTOR pathway and lead to cellular dysregulation. Corresponding proteins from the closely related dengue virus do not have the same effect on neurogenesis. Thus, our study highlights ZIKV NS4A and NS4B as candidate determinants of viral pathogenesis and identifies a mechanism of action for their effects, suggesting potential targets for anti-ZIKV therapeutic intervention.

Indexed as

AutophagyNeurogenesisAnimalsFetusHEK293 CellsHeLa CellsHumansMiceNeural Stem CellsProto-Oncogene Proteins c-aktSignal TransductionSpheroids, CellularTOR Serine-Threonine KinasesViral Nonstructural ProteinsZika VirusZika Virus InfectionNS4A protein, flavivirusNS4B protein, flavivirusProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesViral Nonstructural Proteins

Identifiers

PMID27524440
PMCPMC5144538
OpenAlexW2507412157

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.