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 QinKimberly M. Christian, Pei Yong Shi, Mingjiang Xu, Menghang Xia, Wei Zheng, Hao Wu, Hongjun Song, Hengli Tang, Guo Li Ming, Peng Jin

Research output: Contribution to journalArticle

80 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8610-8620
Number of pages11
JournalNucleic Acids Research
Volume44
Issue number18
DOIs
StatePublished - Oct 14 2016

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ASJC Scopus subject areas

  • Genetics

Cite this

Zhang, F., Hammack, C., Ogden, S. C., Cheng, Y., Lee, E. M., Wen, Z., Qian, X., Nguyen, H. N., Li, Y., Yao, B., Xu, M., Xu, T., Chen, L., Wang, Z., Feng, H., Huang, W. K., Yoon, K. J., Shan, C., Huang, L., ... Jin, P. (2016). Molecular signatures associated with ZIKV exposure in human cortical neural progenitors. Nucleic Acids Research, 44(18), 8610-8620. https://doi.org/10.1093/nar/gkw765