PROJECT SUMMARY: Zika virus (ZIKV) is a flavivirus that has recently caused a large-scale outbreak in South and Central America, and it continues to spread into new geographic areas. ZIKV attacks the nervous system in humans, in utero and in adults, causing diseases ranging from microcephaly to Guillain-Barre syndrome. In both mice and humans, maternal antibodies are transferred from mother to offspring through the placenta. Because ZIKV circulates in many regions around the world where the related flavivirus, dengue virus (DENV), circulates, children born to DENV-immune mothers will have circulating DENV antibodies at the time of birth. We recently showed that cross-reactive DENV antibodies can enhance ZIKV pathogenesis in vivo. However, the extent to which maternal DENV-specific antibodies impacts neonatal ZIKV infection is unknown. We hypothesize that maternally-transferred DENV-specific antibodies enhance ZIKV damage to the neonates. In this application, we will study antibody-dependent enhancement (ADE) of ZIKV pathogenesis and its effects on development in neonatal mice.