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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
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 microcephaly, with potential for further exploration of the underlying mechanisms and management of ZIKV-related pathological effects during brain development.
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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 |
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2016-06-09 |
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摘要: |
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 microcephaly, with potential for further exploration of the underlying mechanisms and management of ZIKV-related pathological effects during brain development. |
英文摘要: |
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 microcephaly, with potential for further exploration of the underlying mechanisms and management of ZIKV-related pathological effects during brain development. |
刊物名称: |
Cell Stem Cell |
英文刊物名称: |
Cell Stem Cell |
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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 |
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