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. This unmet medical need is partly due to the fact that very little is known about the molecular mechanisms governing ZIKV pathogenesis.
Addressing these questions is challenging since it requires the use of animal models (such as mice) which are limited in terms of genetic manipulation, developmental studies 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, while its development is very fast, cell population imaging in the whole larva is convenient because of its optical transparency. Moreover, it is easy to genetically manipulate to invalidate genes and to follow the fate of specific cell types during development and thus, to closely evaluate the impact of given proteins, drugs or pathogens on neurodevelopment. Most importantly, introduction of ZIKV into the embryo leads to severe neurodevelopmental defects while ZIKV accumulates in the brain and the spinal cord, hence partly mirroring the symptoms in humans.
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. Dr. Chatel-Chaix will characterize the nervous cell populations impacted by ZIKV infection and study the viral determinants required for neurovirulence. The model may emerge as an easy-to-handle and flexible tool to genetically address host determinants of ZIKV neuropathogenesis and to quickly screen antiviral drug candidates in vivo.