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Molecular signatures associated with ZIKV exposure in human cortical neural progenitors

View ORCID ProfileFeiran 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, View ORCID ProfileHongjun Song, Hengli Tang, View ORCID ProfileGuo-Li Ming, Peng Jin
doi: https://doi.org/10.1101/071183
Feiran Zhang
1Department of Human Genetics, School of Medicine, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
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Christy Hammack
2Department of Biological Science, Florida State University, Tallahassee, FL, 32306, USA.
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Sarah C. Ogden
2Department of Biological Science, Florida State University, Tallahassee, FL, 32306, USA.
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Yichen Cheng
2Department of Biological Science, Florida State University, Tallahassee, FL, 32306, USA.
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Emily M. Lee
2Department of Biological Science, Florida State University, Tallahassee, FL, 32306, USA.
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Zhexing Wen
3Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
4Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
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Xuyu Qian
3Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
5Biomedical Engineering Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
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Ha Nam Nguyen
3Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
4Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
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Yujing Li
1Department of Human Genetics, School of Medicine, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
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Bing Yao
1Department of Human Genetics, School of Medicine, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
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Miao Xu
6National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD, 20892, USA.
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Tianlei Xu
7Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
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Li Chen
7Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
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Zhiqin Wang
1Department of Human Genetics, School of Medicine, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
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Hao Feng
7Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
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Wei-Kai Huang
3Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
8Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
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Ki-jun Yoon
3Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
4Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
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Chao Shan
9Department of Biochemistry & Molecular Biology, Department of Pharmacology & Toxicology, Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, 77555, USA.
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Luoxiu Huang
1Department of Human Genetics, School of Medicine, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
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Zhaohui Qin
7Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
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Kimberly M. Christian
3Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
4Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
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Pei-Yong Shi
9Department of Biochemistry & Molecular Biology, Department of Pharmacology & Toxicology, Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, 77555, USA.
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Mingjiang Xu
10Sylvester Comprehensive Cancer Center, Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
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Menghang Xia
6National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD, 20892, USA.
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Wei Zheng
6National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD, 20892, USA.
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Hao Wu
7Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
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Hongjun Song
3Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
4Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
11The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
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  • For correspondence: peng.jin@emory.edu
Hengli Tang
2Department of Biological Science, Florida State University, Tallahassee, FL, 32306, USA.
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  • For correspondence: peng.jin@emory.edu
Guo-Li Ming
3Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
4Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
11The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
12Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
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  • For correspondence: peng.jin@emory.edu
Peng Jin
1Department of Human Genetics, School of Medicine, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
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  • For correspondence: peng.jin@emory.edu
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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.

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Posted August 23, 2016.
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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
bioRxiv 071183; doi: https://doi.org/10.1101/071183
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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
bioRxiv 071183; doi: https://doi.org/10.1101/071183

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