2. Academic Validation
  3. Molecular signatures associated with ZIKV exposure in human cortical neural progenitors

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.
Feiran Zhang 1,  Christy Hammack 2,  Sarah C Ogden 2,  Yichen Cheng 2,  Emily M Lee 2,  Zhexing Wen 3,  Xuyu Qian 4,  Ha Nam Nguyen 5,  Yujing Li 1,  Bing Yao 1,  Miao Xu 6,  Tianlei Xu 7,  Li Chen 7,  Zhiqin Wang 1,  Hao Feng 7,  Wei-Kai Huang 8,  Ki-Jun Yoon 5,  Chao Shan 9,  Luoxiu Huang 1,  Zhaohui Qin 7,  Kimberly M Christian 5,  Pei-Yong Shi 9,  Mingjiang Xu 10,  Menghang Xia 6,  Wei Zheng 6,  Hao Wu 7,  Hongjun Song 11,  Hengli Tang 12,  Guo-Li Ming 13,  Peng Jin 14
Affiliations

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 [email protected].
  • 12 Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA [email protected].
  • 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 [email protected].
  • 14 Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA [email protected].
PMID: 27580721 DOI: 10.1093/nar/gkw765
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.

Figures
Products