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沙发
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发表于 2017-10-4 17:07:51
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A single mutation in the prM protein of Zika virus contributes to fetal microcephaly
Ling Yuan1,2,*, Xing-Yao Huang3,*, Zhong-Yu Liu3,*, Feng Zhang1,2,*, Xing-Liang Zhu1,2,*, Jiu-Yang Yu3,*, Xue Ji3, Yan-Peng Xu3, Guanghui Li1,2, Cui Li1,2, Hong-Jiang Wang3, Yong-Qiang Deng3, Menghua Wu4, Meng-Li Cheng3,5, Qing Ye3, Dong-Yang Xie3,5, Xiao-Feng Li3, Xiangxi Wang6, Weifeng Shi7, Baoyang Hu4, Pei-Yong Shi8, Zhiheng Xu1,2,9,†, Cheng-Feng Qin
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.
http://science.sciencemag.org/co ... /27/science.aam7120 |
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