Consequences of congenital Zika virus infection

Abstract

The 2015 Zika virus (ZIKV) epidemic in the Americas led to the discovery that ZIKV causes congenital abnormalities including microcephaly, intrauterine growth restriction, and eye disease that can result in blindness. Studies in animal models and human organoid cultures, together with human epidemiological studies, have shown that ZIKV crosses the placenta and subsequently replicates within fetal tissues including the developing brain. Preferential infection of neural cell precursors causes damage to the developing fetal brain. However, a majority of congenitally infected humans do not develop microcephaly or other overt congenital abnormalities, so longitudinal epidemiological studies are necessary to more completely define the long-term consequences of in utero ZIKV infection.

Figure 1. Consequences of transplacental ZIKV infection

Maternal infection may be acquired either by mosquito or via sexual transmission. Maternal viremia leads to transplacental infection. Placental damage by ZIKV may contribute to placental insufficiency, IUGR, and fetal demise. Severe infection of fetal tissues likely causes microcephaly, blindness, and also fetal demise. Whether placental factors also contribute to microcephaly is not well established. Animal models of congenital ZIKV infection, along with human epidemiological studies, suggest that clinical outcomes are strongly influenced by gestational age at the time of infection [65,66].