Infection with Zika virus during pregnancy can lead to severe birth defects in humans, including microcephaly. Zika has two major lineages – the Asian lineage, which has been associated with birth defects, and the African lineage, which has not – but the relative effects of each strain on brain development, and the effects of the related dengue virus that co-circulates with Zika, have not been addressed. On p. 4114, Jian-Fu Chen and colleagues address this problem by performing intracerebral inoculation with Zika and dengue virus on embryonic mouse brains and comparing their effects on neural development. They show that both dengue and Zika viruses cause microcephaly through impaired neural progenitor proliferation and increased neuronal apoptosis, though the effect is much greater for Zika than dengue. Surprisingly, given the apparent absence of virus-related pathology in affected human populations, the African strain grows faster and causes greater progenitor and neuronal cell death, and higher postnatal mortality, than the Asian lineage. This study generates insights into the neurodevelopmental phenotypes generated by these viruses, and provides a foundation for future investigations into the molecular and genetic causes of Zika pathogenesis.
