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

Research output: Contribution to journalArticle

199 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 languageEnglish (US)
Pages (from-to)933-936
Number of pages4
JournalScience
Volume358
Issue number6365
DOIs
StatePublished - Nov 17 2017

ASJC Scopus subject areas

  • General

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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