Molecular signatures associated with ZIKV exposure in human cortical neural progenitors

作者:Zhang Feiran; Hammack Christy; Ogden Sarah C; Cheng Yichen; Lee Emily M; Wen Zhexing; Qian Xuyu; Ha Nam Nguyen; Li Yujing; Yao Bing; Xu Miao; Xu Tianlei; Chen Li; Wang Zhiqin; Feng Hao; Huang Wei Kai; Yoon Ki jun; Shan Chao; Huang Luoxiu; Qin Zhaohui; Christian Kimberly M; Shi Pei Yong; Xu Mingjiang; Xia Menghang; Zheng Wei; Wu Hao; Song Hongjun*; Tang Hengli*; Ming Guo Li*; Jin Peng*
来源:Nucleic Acids Research, 2016, 44(18): 8610-8620.
DOI:10.1093/nar/gkw765

摘要

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.

  • 出版日期2016-10-14