Human cytomegalovirus (HCMV) is the most common cause of congenital infection and neurodevelopmental disease worldwide, yet no reliable prenatal markers for disease have been identified. In this research project we will develop and employ a novel single-cell-based approach to uncover the unique responses of maternal and fetal cells to HCMV infection, within the authentic tissue complexity of the placenta and in clinical samples from natural congenital infections. We will correlate the observed patterns with congenital HCMV disease outcome, paving the way for prenatal prediction of the risk for congenital HCMV-induced defects in newborns.