HCMV infection mitigate the ability of placental EVs to potentiate neurogenesis by altering their miRNA landscape

Human cytomegalovirus (HCMV) is the most common virus transmitted in utero and a leading cause of infectious brain malformations and deafness, yet prognosis methods remain unreliable. Although certain central nervous system lesions caused by HCMV are explained, the neuropathogenesis of congenital infection remains poorly understood. The placenta, a key target of HCMV, plays a critical role during infection due to its involvement in maternal-fetal exchanges, particularly via the secretion of extracellular vesicles (EVs). Placental EVs mediate maternal-fetal communication, carrying proteins and RNAs, including microRNAs, that influence placental function, maternal immune tolerance, and viral defense. Our study explored the effects of placental EVs on fetal neural stem cell phenotype, demonstrating that EVs secreted from HCMV-infected placenta alter neurogenesis. Analysis of EV microRNA profiles revealed infection-induced alterations with predicted interference in brain development pathways. These findings highlight the critical role of placental EVs in fetal brain development and their contribution to HCMV neuropathogenesis.