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 & 3 others Pei-Yong Shi, Zhiheng Xu, Cheng Feng Qin

Research output: Contribution to journalArticle

140 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalScience
DOIs
StateAccepted/In press - Sep 28 2017

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Microcephaly
Mutation
Proteins
Stem Cells
Polynesia
Polyproteins
Asparagine
Infant Mortality
Serine
Disease Outbreaks
Fetus
Zika Virus
Incidence

ASJC Scopus subject areas

  • General

Cite this

Yuan, L., Huang, X. Y., Liu, Z. Y., Zhang, F., Zhu, X. L., Yu, J. Y., ... Qin, C. F. (Accepted/In press). A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. Science, 1-9. https://doi.org/10.1126/science.aam7120

A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. / Yuan, Ling; Huang, Xing Yao; Liu, Zhong Yu; Zhang, Feng; Zhu, Xing Liang; Yu, Jiu Yang; Ji, Xue; Xu, Yan Peng; Li, Guanghui; Li, Cui; Wang, Hong Jiang; Deng, Yong Qiang; Wu, Menghua; Cheng, Meng Li; Ye, Qing; Xie, Dong Yang; Li, Xiao Feng; Wang, Xiangxi; Shi, Weifeng; Hu, Baoyang; Shi, Pei-Yong; Xu, Zhiheng; Qin, Cheng Feng.

In: Science, 28.09.2017, p. 1-9.

Research output: Contribution to journalArticle

Yuan, L, Huang, XY, Liu, ZY, Zhang, F, Zhu, XL, Yu, JY, Ji, X, Xu, YP, Li, G, Li, C, Wang, HJ, Deng, YQ, Wu, M, Cheng, ML, Ye, Q, Xie, DY, Li, XF, Wang, X, Shi, W, Hu, B, Shi, P-Y, Xu, Z & Qin, CF 2017, 'A single mutation in the prM protein of Zika virus contributes to fetal microcephaly', Science, pp. 1-9. https://doi.org/10.1126/science.aam7120
Yuan, Ling ; Huang, Xing Yao ; Liu, Zhong Yu ; Zhang, Feng ; Zhu, Xing Liang ; Yu, Jiu Yang ; Ji, Xue ; Xu, Yan Peng ; Li, Guanghui ; Li, Cui ; Wang, Hong Jiang ; Deng, Yong Qiang ; Wu, Menghua ; Cheng, Meng Li ; Ye, Qing ; Xie, Dong Yang ; Li, Xiao Feng ; Wang, Xiangxi ; Shi, Weifeng ; Hu, Baoyang ; Shi, Pei-Yong ; Xu, Zhiheng ; Qin, Cheng Feng. / A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. In: Science. 2017 ; pp. 1-9.
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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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AU - Zhu, Xing Liang

AU - Yu, Jiu Yang

AU - Ji, Xue

AU - Xu, Yan Peng

AU - Li, Guanghui

AU - Li, Cui

AU - Wang, Hong Jiang

AU - Deng, Yong Qiang

AU - Wu, Menghua

AU - Cheng, Meng Li

AU - Ye, Qing

AU - Xie, Dong Yang

AU - Li, Xiao Feng

AU - Wang, Xiangxi

AU - Shi, Weifeng

AU - Hu, Baoyang

AU - Shi, Pei-Yong

AU - Xu, Zhiheng

AU - Qin, Cheng Feng

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