|
Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice
Cui Li,Dan Xu,Qing Ye,Shuai Hong,Yisheng Jiang,Xinyi Liu,Nana Zhang,Lei Shi,Cheng-Feng Qin,Zhiheng Xu
Cell Stem Cell
Abstract
Highlights •Zika virus (ZIKV) replicates very efficiently in embryonic mouse brain •ZIKV infects neural progenitor cells (NPCs) and causes microcephaly •ZIKV infection leads to NPC cell-cycle arrest and defects in differentiation •ZIKV infection induces immune response in brain and apoptosis of post-mitotic neurons Summary The link between Zika virus (ZIKV) infection and microcephaly has raised urgent global alarm. The historical African ZIKV MR766 was recently shown to infect cultured human neural precursor cells (NPCs), but unlike the contemporary ZIKV strains, it is not believed to cause microcephaly. Here we investigated whether the Asian ZIKV strain SZ01 could infect NPCs in vivo and affect brain development. We found that SZ01 replicates efficiently in embryonic mouse brain by directly targeting different neuronal linages. ZIKV infection leads to cell-cycle arrest, apoptosis, and inhibition of NPC differentiation, resulting in cortical thinning and microcephaly. Global gene expression analysis of infected brains reveals upregulation of candidate flavirus entry receptors and dysregulation of genes associated with immune response, apoptosis, and microcephaly. Our model provides evidence for a direct link between Zika virus infection and microcepahly, with potential for further exploration of the underlying mechanisms.
|
论文编号: |
DOI:10.1016/j.stem.2016.04.017 |
论文题目: |
Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice |
英文论文题目: |
Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice |
第一作者: |
Cui Li,Dan Xu,Qing Ye,Shuai Hong,Yisheng Jiang,Xinyi Liu,Nana Zhang,Lei Shi,Cheng-Feng Qin,Zhiheng Xu |
英文第一作者: |
Cui Li,Dan Xu,Qing Ye,Shuai Hong,Yisheng Jiang,Xinyi Liu,Nana Zhang,Lei Shi,Cheng-Feng Qin,Zhiheng Xu |
联系作者: |
|
英文联系作者: |
|
外单位作者单位: |
|
英文外单位作者单位: |
|
发表年度: |
2016-05-12 |
卷: |
|
期: |
|
页码: |
|
摘要: |
Highlights •Zika virus (ZIKV) replicates very efficiently in embryonic mouse brain •ZIKV infects neural progenitor cells (NPCs) and causes microcephaly •ZIKV infection leads to NPC cell-cycle arrest and defects in differentiation •ZIKV infection induces immune response in brain and apoptosis of post-mitotic neurons Summary The link between Zika virus (ZIKV) infection and microcephaly has raised urgent global alarm. The historical African ZIKV MR766 was recently shown to infect cultured human neural precursor cells (NPCs), but unlike the contemporary ZIKV strains, it is not believed to cause microcephaly. Here we investigated whether the Asian ZIKV strain SZ01 could infect NPCs in vivo and affect brain development. We found that SZ01 replicates efficiently in embryonic mouse brain by directly targeting different neuronal linages. ZIKV infection leads to cell-cycle arrest, apoptosis, and inhibition of NPC differentiation, resulting in cortical thinning and microcephaly. Global gene expression analysis of infected brains reveals upregulation of candidate flavirus entry receptors and dysregulation of genes associated with immune response, apoptosis, and microcephaly. Our model provides evidence for a direct link between Zika virus infection and microcepahly, with potential for further exploration of the underlying mechanisms. |
英文摘要: |
Highlights •Zika virus (ZIKV) replicates very efficiently in embryonic mouse brain •ZIKV infects neural progenitor cells (NPCs) and causes microcephaly •ZIKV infection leads to NPC cell-cycle arrest and defects in differentiation •ZIKV infection induces immune response in brain and apoptosis of post-mitotic neurons Summary The link between Zika virus (ZIKV) infection and microcephaly has raised urgent global alarm. The historical African ZIKV MR766 was recently shown to infect cultured human neural precursor cells (NPCs), but unlike the contemporary ZIKV strains, it is not believed to cause microcephaly. Here we investigated whether the Asian ZIKV strain SZ01 could infect NPCs in vivo and affect brain development. We found that SZ01 replicates efficiently in embryonic mouse brain by directly targeting different neuronal linages. ZIKV infection leads to cell-cycle arrest, apoptosis, and inhibition of NPC differentiation, resulting in cortical thinning and microcephaly. Global gene expression analysis of infected brains reveals upregulation of candidate flavirus entry receptors and dysregulation of genes associated with immune response, apoptosis, and microcephaly. Our model provides evidence for a direct link between Zika virus infection and microcepahly, with potential for further exploration of the underlying mechanisms. |
刊物名称: |
Cell Stem Cell |
英文刊物名称: |
Cell Stem Cell |
论文全文: |
|
英文论文全文: |
|
全文链接: |
|
其它备注: |
Cui Li,Dan Xu,Qing Ye,Shuai Hong,Yisheng Jiang,Xinyi Liu,Nana Zhang,Lei Shi,Cheng-Feng Qin,Zhiheng Xu. Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice. Cell Stem Cell. DOI:10.1016/j.stem.2016.04.017 |
英文其它备注: |
|
学科: |
|
英文学科: |
|
影响因子: |
|
第一作者所在部门: |
|
英文第一作者所在部门: |
|
论文出处: |
|
英文论文出处: |
|
论文类别: |
|
英文论文类别: |
|
参与作者: |
|
英文参与作者: |
|
|