Immune mechanisms of congenital Zika syndrome

Zika virus (ZIKV) infection during pregnancy can adversely affect mother and child. ZIKV can vertically transmit from mother to fetus, especially during early pregnancy, to cause congenital Zika syndrome (CZS), which includes microcephaly, ocular and musculoskeletal defects, and other disorders. Whereas human clinical studies have provided crucial insights into how ZIKV affects pregnancy, animal models have uncovered mechanisms of fetal disease. This Review discusses fetal immunological factors that contribute to or protect from CZS, as well as the interplay between maternal and fetal immunity, viral molecular factors, maternal nutrition, and metabolic changes to fetal ZIKV infection and disease outcomes. We also consider how factors like preexisting flavivirus immunity and gene polymorphisms may affect CZS risk, with implications for vaccine and therapeutic development. There are insights to be gained from studying ZIKV disease for our improved understanding of congenital infections and the functioning of the immune system in early life.