Deciphering the role of microglia in Zika virus-induced neuroinflammation and pathogenesis during fetal brain development

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 microcephaly in the infant. Most importantly, no antiviral therapies or vaccine against ZIKV are currently available, as we poorly understand the relative contribution of resident and infiltrating immune cells and neural progenitor cells to the disease. Relying on our wide expertise in virology and neurodevelopment, this proposal aims to better understand ZIKV pathogenesis in the developing brain in vivo by taking advantage of our innovative in utero mouse fetal brain infection model recently developed by our team. We will characterize the contribution of brain-specific macrophages (named microglia) to ZIKV-induced neuroinflammation and microcephaly. This project will contribute to a better understanding of the etiology of ZIKV neuropathogenesis and might identify promising antiviral targets for drug development.