Abstract
Zika virus (ZIKV) infection represents a critical threat to maternal–fetal health due to its ability to cross the placental barrier, converting this normally protective organ into a direct target of viral infection. This study examines the mechanisms by which ZIKV infects placental cells, including trophoblasts and Hofbauer macrophages, through the engagement of specific cellular receptors such as AXL and T‐cell immunoglobulin and mucin (TIM), while simultaneously evading host immune defenses. Although the placental immune system employs interferon signaling and innate immune cells to restrict viral replication, ZIKV disrupts these pathways, promoting chronic inflammation and structural damage within placental tissue. These morphofunctional alterations impair fetal nutrient exchange and facilitate vertical transmission, leading to severe adverse outcomes such as congenital Zika syndrome (CZS), intrauterine growth restriction, and preterm birth. Importantly, pregnancy outcomes appear to depend on a delicate balance between the timing of maternal infection and the effectiveness of the local immune response. Finally, this study highlights the need for advanced molecular approaches and “omics” technologies to address existing knowledge gaps regarding viral variability and to inform the development of future therapeutic strategies aimed at preventing fetal transmission.