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Modelling Zika virus infection of the developing human brain in vitro using stem cell-derived cerebral organoids

Salick, Max and Wells, Michael F and Eggan, Kevin and Kaykas, Ajamete (2017) Modelling Zika virus infection of the developing human brain in vitro using stem cell-derived cerebral organoids. Journal of visualized experiments : JoVE (127). ISSN 1940-087X

Abstract

The recent emergence of Zika virus (ZIKV) in susceptible populations has led to an abrupt increase in microcephaly and other neurodevelopmental conditions in newborn infants. While mosquitos are the main route of viral transmission, it has also been shown to spread via sexual contact and vertical mother-to-fetus transmission. In this latter case of transmission, due to the unique viral tropism of ZIKV, the virus is believed to predominantly target the neural progenitor cells (NPCs) of the developing brain.

Here we present a method for modeling ZIKV infection, and the resulting microcephaly, that occur when human cerebral organoids are exposed to live ZIKV. The organoids display high levels of virus within their neural progenitor population, and exhibit severe cell death and microcephaly over time. This three dimensional cerebral organoid model allows researchers to conduct species-matched experiments to observe and potentially intervene with ZIKV infection of the developing human brain. The model provides improved relevance over standard two dimensional methods, and contains human-specific cellular architecture and protein expression that are not possible in animal models.

Item Type: Article
Date Deposited: 19 Jan 2018 00:45
Last Modified: 19 Jan 2018 00:45
URI: https://oak.novartis.com/id/eprint/32894

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