Studying Zika virus neuropathogenesis and its determinants in vivo using a newly engineered zebrafish infection model

Infections with Zika virus (ZIKV) constitute a major global public health concern worldwide. Indeed, the recent ZIKV outbreak in the Americas revealed that infection of pregnant women can lead to congenital transmission, infection within the fetal developing brain and eventually to microcephaly in the infant. Most importantly, no antiviral therapies or vaccine against ZIKV are currently available, as we poorly understand how the disease develops. Addressing these questions is challenging since it requires the use of animal models (such as mice) which are limited in terms of genetic manipulation, access to infected regions of the developing brain and number of handled individuals. In that respect, the zebrafish model has emerged as a very powerful animal model to study vertebrate brain development in vivo. Indeed, Zebrafish are small fish which develop very fast and have a transparent body. This means that brain cells can be easily visualized and that it is possible to observe the impacts of genetic manipulations and infections. Most importantly, ZIKV symptoms and developmental defects in humans can be replicated in zebrafish larvae. Relying on our wide expertise in virology and neurodevelopment, this proposal aims at better understanding ZIKV neuropathogenesis in vivo by taking advantage of this novel infection animal model based on zebrafish developed by our laboratory. We will characterize the nervous cell populations impacted by ZIKV infection and study the viral determinants required for neurovirulence. Our model may emerge as an easy-to-handle and flexible tool to study the host determinants of ZIKV neuropathogenesis and to quickly screen antiviral drug candidates in vivo.