Molecular signatures associated with ZIKV exposure in human cortical neural progenitors

Feiran Zhang; Christy Hammack; Sarah C Ogden; Yichen Cheng; Emily M Lee; Zhexing Wen; Xuyu Qian; Ha Nam Nguyen; Yujing Li; Bing Yao; Miao Xu; Tianlei Xu; Li Chen; Zhiqin Wang; Hao Feng; Wei-Kai Huang; Ki-Jun Yoon; Chao Shan; Luoxiu Huang; Zhaohui Qin; Kimberly M Christian; Pei-Yong Shi; Mingjiang Xu; Menghang Xia; Wei Zheng; Hao Wu; Hongjun Song; Hengli Tang; Guo-Li Ming; Peng Jin

doi:10.1093/nar/gkw765

Molecular signatures associated with ZIKV exposure in human cortical neural progenitors

Nucleic Acids Res. 2016 Oct 14;44(18):8610-8620. doi: 10.1093/nar/gkw765. Epub 2016 Aug 31.

Authors

Feiran Zhang¹, Christy Hammack², Sarah C Ogden², Yichen Cheng², Emily M Lee², Zhexing Wen³, Xuyu Qian⁴, Ha Nam Nguyen⁵, Yujing Li¹, Bing Yao¹, Miao Xu⁶, Tianlei Xu⁷, Li Chen⁷, Zhiqin Wang¹, Hao Feng⁷, Wei-Kai Huang⁸, Ki-Jun Yoon⁵, Chao Shan⁹, Luoxiu Huang¹, Zhaohui Qin⁷, Kimberly M Christian⁵, Pei-Yong Shi⁹, Mingjiang Xu¹⁰, Menghang Xia⁶, Wei Zheng⁶, Hao Wu⁷, Hongjun Song¹¹, Hengli Tang¹², Guo-Li Ming¹³, Peng Jin¹⁴

Affiliations

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 ZIKV^C, African ZIKV^M, 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, ZIKV^C, but not ZIKV^M, induces upregulation of viral response genes and TP53. P53 inhibitors can block the apoptosis induced by both ZIKV^C and ZIKV^M in hNPCs, with higher potency against ZIKV^C-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.

MeSH terms

Cell Death / genetics
Cell Line
Cerebral Cortex / cytology*
DNA Repair / genetics
DNA Replication / genetics
Dengue Virus / physiology
Gene Expression Profiling*
Humans
Neural Stem Cells / metabolism*
Neural Stem Cells / virology*
Signal Transduction / genetics
Species Specificity
Tumor Suppressor Protein p53 / metabolism
Up-Regulation / genetics
Zika Virus / physiology*
Zika Virus Infection / genetics*
Zika Virus Infection / virology

Substances

Tumor Suppressor Protein p53

Abstract

MeSH terms

Substances

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