Molecular signatures associated with ZIKV exposure in human cortical neural progenitors

• Published in: Nucleic acids research Vol. 44; no. 18; pp. 8610 - 8620
• Main Authors: Zhang, Feiran, Hammack, Christy, Ogden, Sarah C., Cheng, Yichen, Lee, Emily M., Wen, Zhexing, Qian, Xuyu, Nguyen, Ha Nam, 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
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 14.10.2016
• Subjects: Cell Death - genetics; Cell Line; Cerebral Cortex - cytology; Data Resources and Analyses; Dengue Virus - physiology; DNA Repair - genetics; DNA Replication - genetics; 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
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkw765

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