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

doi:10.1093/nar/gkw765

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

145 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 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.

Original language	English (US)
Pages (from-to)	8610-8620
Number of pages	11
Journal	Nucleic acids research
Volume	44
Issue number	18
DOIs	https://doi.org/10.1093/nar/gkw765
State	Published - Oct 14 2016

ASJC Scopus subject areas

Genetics

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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

Zhang, F, Hammack, C, Ogden, SC, Cheng, Y, Lee, EM, Wen, Z, Qian, X, Nguyen, HN, Li, Y, Yao, B, Xu, M, Xu, T, Chen, L, Wang, Z, Feng, H, Huang, WK, Yoon, KJ, Shan, C, Huang, L, Qin, Z, Christian, KM, Shi, PY, Xu, M, Xia, M, Zheng, W, Wu, H, Song, H, Tang, H, Ming, GL & Jin, P 2016, 'Molecular signatures associated with ZIKV exposure in human cortical neural progenitors', Nucleic acids research, vol. 44, no. 18, pp. 8610-8620. https://doi.org/10.1093/nar/gkw765

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title = "Molecular signatures associated with ZIKV exposure in human cortical neural progenitors",

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.",

author = "Feiran Zhang and Christy Hammack and Ogden, {Sarah C.} and Yichen Cheng and Lee, {Emily M.} and Zhexing Wen and Xuyu Qian and Nguyen, {Ha Nam} and Yujing Li and Bing Yao and Miao Xu and Tianlei Xu and Li Chen and Zhiqin Wang and Hao Feng and Huang, {Wei Kai} and Yoon, {Ki Jun} and Chao Shan and Luoxiu Huang and Zhaohui Qin and Christian, {Kimberly M.} and Shi, {Pei Yong} and Mingjiang Xu and Menghang Xia and Wei Zheng and Hao Wu and Hongjun Song and Hengli Tang and Ming, {Guo Li} and Peng Jin",

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doi = "10.1093/nar/gkw765",

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AU - Zhang, Feiran

AU - Hammack, Christy

AU - Ogden, Sarah C.

AU - Cheng, Yichen

AU - Lee, Emily M.

AU - Wen, Zhexing

AU - Qian, Xuyu

AU - Nguyen, Ha Nam

AU - Li, Yujing

AU - Yao, Bing

AU - Xu, Miao

AU - Xu, Tianlei

AU - Chen, Li

AU - Wang, Zhiqin

AU - Feng, Hao

AU - Huang, Wei Kai

AU - Yoon, Ki Jun

AU - Shan, Chao

AU - Huang, Luoxiu

AU - Qin, Zhaohui

AU - Christian, Kimberly M.

AU - Shi, Pei Yong

AU - Xu, Mingjiang

AU - Xia, Menghang

AU - Zheng, Wei

AU - Wu, Hao

AU - Song, Hongjun

AU - Tang, Hengli

AU - Ming, Guo Li

AU - Jin, Peng

PY - 2016/10/14

Y1 - 2016/10/14

N2 - 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.

AB - 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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Molecular signatures associated with ZIKV exposure in human cortical neural progenitors

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