A Single Mutation in Zika Virus Results in Microcephaly

One single genetic change, likely acquired in 2013, gave the Zika virus the ability to cause severe fetal microcephaly, researchers report. The findings clarify how a virus evolved from an innocuous illness into a pathogen of global concern. Since 2016, Zika virus epidemics in the Americas have been declared a public health emergency by the World Health Organization, and scientists haven't been able to determine why the virus transitioned from sporadically causing mild infections to triggering severe neurological syndromes.

By comparing contemporary Zika virus strains from the 2015 and 2016 South American epidemics with an ancestral Cambodian virus that was circulating in 2010, Ling Yuan and colleagues homed in on one critical mutation that conferred the ability to cause microcephaly in mouse models of fetal infection. That one change, S139N, which replaced a serine amino acid with an arginine at the 139th position of a structural protein called prM within the pathogen's protective coat, also made the virus more lethal to human neuron precursor cells in culture compared with the ancestral form. Zika virus accumulated numerous changes throughout its genome between 2010 and 2016, which is why the researchers constructed and tested seven different mutant viruses - of all the variants, S139N caused substantially more severe microcephaly and embryonic lethality in mouse models. Evolutionary analyses revealed that the S139N change likely arose sometime around 2013, which coincides with initial reports of microcephaly and Guillain-Barre syndrome.