This article is more than 5 years old. Information may no longer be current.
Single mutation in Zika virus causes microcephaly
Researchers identified a single genetic mutation in Zika virus that significantly enhances its infectivity and results in microcephaly.
“Our findings offer an explanation for the unexpected causal link of [Zika virus (ZIKV)] to microcephaly, and will help understand how ZIKV evolved from an innocuous mosquito-borne virus into a congenital pathogen with global impact,” Ling Yuan of the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences, and colleagues wrote in Science.
WHO declared Zika a Public Health Emergency of International Concern in 2016 after an unusual rise in cases of microcephaly and other neurological disorders was linked to the virus. Before then, Zika was a considered a usually asymptomatic and mild disease. Although a previous study linked a spontaneous mutation to increased infectivity and ZIKV prevalence in mosquitoes, it was unclear whether the mutation was associated with complications such as congenital Zika syndrome.
In a new study, Yuan and colleagues compared three contemporary ZIKV strains (MTQ/2015, VEN/2016 and SAM/2016) isolated in 2015 and 2016 with an Asian ancestral strain (CAM/2010) isolated in Cambodia in 2010. They found evidence that the contemporary strains were more neurovirulent than CAM/2010 and had acquired multiple substitutions at different time points. A single mutation in the prM protein known as S139N enhanced viral replication and caused more extensive cell death in human neuronal progenitor cells (NPCs) compared with the ancestral form of the virus.
The researchers estimated that the mutation first emerged in May 2013, a few months before the ZIKV outbreak in French Polynesia.
“The emergence of the S139N substitution correlates with the emergence of reports of microcephaly and other severe neurological abnormalities, including Guillain-Barré syndrome, they wrote.” – by Stephanie Viguers
Disclosure: Yuan reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.