Preventive effects of folic acid on Zika virus-associated poor pregnancy outcomes in immunocompromised micePLOS Pathogens, May 11, 2020
Zika virus (ZIKV) infection may lead to congenital microcephaly and pregnancy loss in pregnant women. In the context of pregnancy, folic acid (FA) supplementation may reduce the risk of abnormal pregnancy outcomes. Intriguingly, FA may have a beneficial effect on the adverse pregnancy outcomes associated with ZIKV infection. Here, we show that FA inhibits ZIKV replication in human umbilical vein endothelial cells (HUVECs) and a cell culture model of blood-placental barrier (BPB). The inhibitory effect of FA against ZIKV infection is associated with FRα-AMPK signaling. Furthermore, treatment with FA reduces pathological features in the placenta, number of fetal resorptions, and stillbirths in two mouse models of in utero ZIKV transmission. Mice with FA treatment showed lower viral burden and better prognostic profiles in the placenta including reduced inflammatory response, and enhanced integrity of BPB. Overall, our findings suggest the preventive role of FA supplementation in ZIKV-associated abnormal pregnancy and warrant nutritional surveillance to evaluate maternal FA status in areas with active ZIKV transmission.
Zika virus (ZIKV) infection in pregnant women may cause a broad spectrum of abnormal pregnancy outcomes. Folic acid (FA) is an essential water-soluble vitamin B required for placental and fetal development to avoid placental abruption, neural tube defects, intrauterine growth restriction, and pregnancy loss. However, the beneficial role of FA in improving clinical presentations with in utero transmission of ZIKV is unknown. We observe that FA treatment increases the level of maternal serum FA and improves feto-placental outcomes in two mouse models of in utero transmission of ZIKV. FA blocks ZIKV transmission in a cell culture model of blood-placental barrier by inhibiting viral replication in endothelial cells. This study may serve as a scientific reference for public health practitioners to evaluate the FA status of pregnant women with ZIKV-infection and the correlation with their pregnancy outcomes.