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Science. 2017 Nov 17;358(6365):933-936. doi: 10.1126/science.aam7120. Epub 2017 Sep 28.

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

Yuan L1,2, Huang XY3, Liu ZY3, Zhang F1,2, Zhu XL1,2, Yu JY3, Ji X3, Xu YP3, Li G1,2, Li C1,2, Wang HJ3, Deng YQ3, Wu M4, Cheng ML3,5, Ye Q3, Xie DY3,5, Li XF3, Wang X6, Shi W7, Hu B4, Shi PY8, Xu Z1,2,9, Qin CF3.

Author information

1
State Key Laboratory of Molecular Developmental Biology, Chinese Academy of Sciences (CAS) Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, CAS, Beijing 100101, China.
2
University of CAS, Beijing 100101, China.
3
Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
4
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, CAS, Beijing 100101, China.
5
Graduate School, Anhui Medical University, Hefei 230032, China.
6
National Laboratory of Macromolecules, Institute of Biophysics, CAS, Beijing 100101, China.
7
Shandong Universities Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases, Taishan Medical College, Taian 271000, China.
8
Department of Biochemistry and Molecular Biology and Department of Pharmacology and Toxicology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA.
9
Parkinson's Disease Center, Beijing Institute for Brain Disorders, Beijing 100101, China.

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.

PMID:
28971967
DOI:
10.1126/science.aam7120
[Indexed for MEDLINE]

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