Zika Virus Can Strongly Infect and Disrupt Secondary Organizers in the Ventricular Zone of the Embryonic Chicken Brain

Abstract

Summary: Zika virus (ZIKV) is associated with severe neurodevelopmental impairments in human fetuses, including microencephaly. Previous reports examining neural progenitor tropism of ZIKV in organoid and animal models did not address whether the virus infects all neural progenitors uniformly. To explore this, ZIKV was injected into the neural tube of 2-day-old chicken embryos, resulting in nonuniform periventricular infection 3 days later. Recurrent foci of intense infection were present at specific signaling centers that influence neuroepithelial patterning at a distance through secretion of morphogens. ZIKV infection reduced transcript levels for 3 morphogens, SHH, BMP7, and FGF8 expressed at the midbrain basal plate, hypothalamic floor plate, and isthmus, respectively. Levels of Patched1, a SHH-pathway downstream gene, were also reduced, and a SHH-dependent cell population in the ventral midbrain was shifted in position. Thus, the diminishment of signaling centers through ZIKV-mediated apoptosis may yield broader, non-cell-autonomous changes in brain patterning. : Zika virus (ZIKV) displays tropism for neural progenitors. Thawani et al. show non-uniform ZIKV infection in the developing chicken brain, with preferential infection of the basal plate and other sources of key signaling molecules. Cell death within these signaling centers may lead to non-cell-autonomous effects on neighboring neuroepithelial patterning. Keywords: Zika virus, microencephaly, tropism, neuromeres, signaling centers, floor plate, basal plate, midbrain, morphogen