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A Single Mutation in the prM Protein of Zika Virus Contributes to Fetal Microcephaly
Ling Yuan, Xing-Yao Huang, Zhong-Yu Liu, Feng Zhang, Xing-Liang Zhu, Jiu-Yang Yu, Xue Ji, Yan-Peng Xu, Guanghui Li, Cui Li, Hong-Jiang Wang, Yong-Qiang Deng, Menghua Wu, Meng-Li Cheng, Qing Ye, Dong-Yang Xie, Xiao-Feng Li, Xiangxi Wang, Weifeng Shi, Baoyang Hu, Pei-Yong Shi, Zhiheng Xu, Cheng-Feng Qin
Science
Abstract
Zika virus (ZIKV) has evolved into a global health threat due to its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated multiple substitutions from their Asian ancestor. Here, we show that a single serine to asparagine substitution (S139N) in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs), led to more significant microcephaly in the mouse fetus, and higher mortality in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics.
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DOI:10.1126/science.aam7120 |
论文题目: |
A Single Mutation in the prM Protein of Zika Virus Contributes to Fetal Microcephaly |
英文论文题目: |
A Single Mutation in the prM Protein of Zika Virus Contributes to Fetal Microcephaly |
第一作者: |
Ling Yuan, Xing-Yao Huang, Zhong-Yu Liu, Feng Zhang, Xing-Liang Zhu, Jiu-Yang Yu, Xue Ji, Yan-Peng Xu, Guanghui Li, Cui Li, Hong-Jiang Wang, Yong-Qiang Deng, Menghua Wu, Meng-Li Cheng, Qing Ye, Dong-Yang Xie, Xiao-Feng Li, Xiangxi Wang, Weifeng Shi, Baoyang Hu, Pei-Yong Shi, Zhiheng Xu, Cheng-Feng Qin |
英文第一作者: |
Ling Yuan, Xing-Yao Huang, Zhong-Yu Liu, Feng Zhang, Xing-Liang Zhu, Jiu-Yang Yu, Xue Ji, Yan-Peng Xu, Guanghui Li, Cui Li, Hong-Jiang Wang, Yong-Qiang Deng, Menghua Wu, Meng-Li Cheng, Qing Ye, Dong-Yang Xie, Xiao-Feng Li, Xiangxi Wang, Weifeng Shi, Baoyang Hu, Pei-Yong Shi, Zhiheng Xu, Cheng-Feng Qin |
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2017-09-30 |
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摘要: |
Zika virus (ZIKV) has evolved into a global health threat due to its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated multiple substitutions from their Asian ancestor. Here, we show that a single serine to asparagine substitution (S139N) in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs), led to more significant microcephaly in the mouse fetus, and higher mortality in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics. |
英文摘要: |
Zika virus (ZIKV) has evolved into a global health threat due to its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated multiple substitutions from their Asian ancestor. Here, we show that a single serine to asparagine substitution (S139N) in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs), led to more significant microcephaly in the mouse fetus, and higher mortality in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics. |
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Science |
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Science |
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其它备注: |
Ling Yuan, Xing-Yao Huang, Zhong-Yu Liu, Feng Zhang, Xing-Liang Zhu, Jiu-Yang Yu, Xue Ji, Yan-Peng Xu, Guanghui Li, Cui Li, Hong-Jiang Wang, Yong-Qiang Deng, Menghua Wu, Meng-Li Cheng, Qing Ye, Dong-Yang Xie, Xiao-Feng Li, Xiangxi Wang, Weifeng Shi, Baoyang Hu, Pei-Yong Shi, Zhiheng Xu, Cheng-Feng Qin. A Single Mutation in the prM Protein of Zika Virus Contributes to Fetal Microcephaly. Science. DOI:10.1126/science.aam7120 |
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