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.

中文翻译：

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寨卡病毒prM蛋白的单个突变有助于胎儿小头畸形

寨卡病毒（ZIKV）由于其与小头畸形的意想不到的因果关系，已演变成一种全球性健康威胁。系统发育分析表明，当代流行毒株已经积累了来自其亚洲祖先的多个替代品。在这里，我们显示病毒多蛋白中的单个丝氨酸到天冬酰胺取代[Ser139→Asn139（S139N）]大大增加了人和小鼠神经祖细胞（NPC）的ZIKV感染力，并导致小鼠胎儿的小头畸形更为严重，以及新生小鼠的更高死亡率。进化分析表明，S139N取代是在2013年法属波利尼西亚爆发之前出现的，在随后传播到美洲期间一直保持稳定。这种功能上的改进使ZIKV对人类NPC更具杀伤力，