Prenatal Zika virus (ZIKV) infection has been linked to pregnancy complications and developmental defects, most notably microcephaly. The causal link between ZIKV infection and congenital brain abnormalities was first recognized in 2016; however, there is serological evidence that ZIKV has circulated for many years. A recent study found that current epidemic strains had become more neurovirulent compared with ancestral strains. To understand this difference, the authors compared the genome sequences of contemporary and ancestral strains and observed a number of amino acid substitutions. They constructed ancestral mutant viruses with these substitutions and found that a single serine-to-asparagine mutation in the viral prM protein enhanced infectivity in human and mouse neural progenitor cells, increased neurovirulence and led to more severe microcephaly in mice. The authors suggest that this single mutation led to the observed increased incidence of microcephaly in the recent ZIKV epidemic.
References
Yuan, L. et al. A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. Science 358, 933–936 (2017)
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York, A. A small change makes a big difference. Nat Rev Microbiol 16, 2 (2018). https://doi.org/10.1038/nrmicro.2017.162
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DOI: https://doi.org/10.1038/nrmicro.2017.162