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

doi:10.1126/science.aam7120

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 HuPei Yong Shi, Zhiheng Xu, Cheng Feng Qin

Biochemistry & Molecular Biology

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

325 Scopus citations

Abstract

Zika virus (ZIKV) has evolved into a global health threat because of 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 [Ser¹³⁹→Asn¹³⁹ (S139N)] in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates 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 language	English (US)
Pages (from-to)	933-936
Number of pages	4
Journal	Science
Volume	358
Issue number	6365
DOIs	https://doi.org/10.1126/science.aam7120
State	Published - Nov 17 2017

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Yuan, L., Huang, X. Y., Liu, Z. Y., Zhang, F., Zhu, X. L., Yu, J. Y., Ji, X., Xu, Y. P., Li, G., Li, C., Wang, H. J., Deng, Y. Q., Wu, M., Cheng, M. L., Ye, Q., Xie, D. Y., Li, X. F., Wang, X., Shi, W., ... Qin, C. F. (2017). A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. Science, 358(6365), 933-936. https://doi.org/10.1126/science.aam7120

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, PY, Xu, Z & Qin, CF 2017, 'A single mutation in the prM protein of Zika virus contributes to fetal microcephaly', Science, vol. 358, no. 6365, pp. 933-936. https://doi.org/10.1126/science.aam7120

@article{abf43451a157451fabef4f64e07af483,

title = "A single mutation in the prM protein of Zika virus contributes to fetal microcephaly",

abstract = "Zika virus (ZIKV) has evolved into a global health threat because of 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 [Ser139→Asn139 (S139N)] in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates 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.",

author = "Ling Yuan and Huang, {Xing Yao} and Liu, {Zhong Yu} and Feng Zhang and Zhu, {Xing Liang} and Yu, {Jiu Yang} and Xue Ji and Xu, {Yan Peng} and Guanghui Li and Cui Li and Wang, {Hong Jiang} and Deng, {Yong Qiang} and Menghua Wu and Cheng, {Meng Li} and Qing Ye and Xie, {Dong Yang} and Li, {Xiao Feng} and Xiangxi Wang and Weifeng Shi and Baoyang Hu and Shi, {Pei Yong} and Zhiheng Xu and Qin, {Cheng Feng}",

note = "Funding Information: We thank A. Davidson (University of Bristol), A.-H. Zheng (CAS), and B. Zhang (CAS) for helpful discussion and critical reagents. This work was supported by the National Natural Science Foundation of China (NSFC) (grants 31770190, 31730108, 31430037, 81661148054, and 81661130162), the National Key Research and Development Project of China (grant 2016YFD0500304), the National Science and Technology Major Project of China (grants 2017ZX09101005, 2014CB942801, and 2017ZX10304402), CAS (grants QYZDJ-SSW-SMC007 and GJHZ1827), the Shanghai Brain-Intelligence Project from the Shanghai Science and Technology Committee (grant 16JC1420500), and the Beijing Brain Project (grant Z161100002616004). C.-F.Q. was supported by an Excellent Young Scientist grant (81522025), a grant from the Innovative Research Group (81621005) from NSFC, and the Newton Advanced Fellowship from the U.K. Academy of Medical Sciences. W.S. was supported by the Taishan Scholars program of Shandong province (grant ts201511056). All data needed to understand and assess the conclusions of this research are available in the main paper and supplementary materials. Publisher Copyright: {\textcopyright} 2017, American Association for the Advancement of Science. All rights reserved.",

year = "2017",

month = nov,

day = "17",

doi = "10.1126/science.aam7120",

language = "English (US)",

volume = "358",

pages = "933--936",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

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TY - JOUR

T1 - A single mutation in the prM protein of Zika virus contributes to fetal microcephaly

AU - Yuan, Ling

AU - Huang, Xing Yao

AU - Liu, Zhong Yu

AU - Zhang, Feng

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

N1 - Funding Information: We thank A. Davidson (University of Bristol), A.-H. Zheng (CAS), and B. Zhang (CAS) for helpful discussion and critical reagents. This work was supported by the National Natural Science Foundation of China (NSFC) (grants 31770190, 31730108, 31430037, 81661148054, and 81661130162), the National Key Research and Development Project of China (grant 2016YFD0500304), the National Science and Technology Major Project of China (grants 2017ZX09101005, 2014CB942801, and 2017ZX10304402), CAS (grants QYZDJ-SSW-SMC007 and GJHZ1827), the Shanghai Brain-Intelligence Project from the Shanghai Science and Technology Committee (grant 16JC1420500), and the Beijing Brain Project (grant Z161100002616004). C.-F.Q. was supported by an Excellent Young Scientist grant (81522025), a grant from the Innovative Research Group (81621005) from NSFC, and the Newton Advanced Fellowship from the U.K. Academy of Medical Sciences. W.S. was supported by the Taishan Scholars program of Shandong province (grant ts201511056). All data needed to understand and assess the conclusions of this research are available in the main paper and supplementary materials. Publisher Copyright: © 2017, American Association for the Advancement of Science. All rights reserved.

PY - 2017/11/17

Y1 - 2017/11/17

N2 - Zika virus (ZIKV) has evolved into a global health threat because of 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 [Ser139→Asn139 (S139N)] in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates 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.

AB - Zika virus (ZIKV) has evolved into a global health threat because of 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 [Ser139→Asn139 (S139N)] in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates 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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DO - 10.1126/science.aam7120

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AN - SCOPUS:85030531753

SN - 0036-8075

VL - 358

SP - 933

EP - 936

JO - Science

JF - Science

IS - 6365

ER -

A single mutation in the prM protein of Zika virus contributes to fetal microcephaly

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