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Nucleic Acids Res. 2016 Oct 14;44(18):8610-8620. Epub 2016 Aug 31.

Molecular signatures associated with ZIKV exposure in human cortical neural progenitors.

Author information

1
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
2
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
3
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Departments of Psychiatry and Behavioral Science, Cell Biology, and Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
4
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Biomedical Engineering Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
5
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
6
National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD 20892, USA.
7
Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, GA 30322, USA.
8
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
9
Department of Biochemistry & Molecular Biology, Department of Pharmacology & Toxicology, Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA.
10
Sylvester Comprehensive Cancer Center, Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
11
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA shongju1@jhmi.edu.
12
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA tang@bio.fsu.edu.
13
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA gming1@jhmi.edu.
14
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA peng.jin@emory.edu.

Abstract

Zika virus (ZIKV) infection causes microcephaly and has been linked to other brain abnormalities. How ZIKV impairs brain development and function is unclear. Here we systematically profiled transcriptomes of human neural progenitor cells exposed to Asian ZIKVC, African ZIKVM, and dengue virus (DENV). In contrast to the robust global transcriptome changes induced by DENV, ZIKV has a more selective and larger impact on expression of genes involved in DNA replication and repair. While overall expression profiles are similar, ZIKVC, but not ZIKVM, induces upregulation of viral response genes and TP53. P53 inhibitors can block the apoptosis induced by both ZIKVC and ZIKVM in hNPCs, with higher potency against ZIKVC-induced apoptosis. Our analyses reveal virus- and strain-specific molecular signatures associated with ZIKV infection. These datasets will help to investigate ZIKV-host interactions and identify neurovirulence determinants of ZIKV.

PMID:
27580721
PMCID:
PMC5063002
DOI:
10.1093/nar/gkw765
[Indexed for MEDLINE]
Free PMC Article

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