In mammals, the placenta is a connection between a mother and a new developing organism. This tissue has a protective function against some microorganisms, transports nutrients, and exchanges gases and excretory substances between the mother and the fetus. Placental tissue is mainly composed of chorionic villi functional units called trophoblasts (cytotrophoblasts, the syncytiotrophoblast, and extravillous trophoblasts). However, some viruses have developed mechanisms that help them invade the placenta, causing various conditions such as necrosis, poor perfusion, and membrane rupture which, in turn, can impact the development of the fetus and put the mother’s health at risk. In this study, we collected the most relevant information about viral infection during pregnancy which can affect both the mother and the fetus, leading to an increase in the probability of vertical transmission. Knowing these mechanisms could be relevant for new research in the maternal–fetal context and may provide options for new therapeutic targets and biomarkers in fetal prognosis.

Infection with Zika virus (ZIKV) is a perinatal health problem and a vertical infection that promotes neurological fetal damage. ZIKV infects different cellular components at the maternal–fetal interface, including umbilical cord endothelial cells (HUVECs). Extracellular vesicles (EVs) are cellular components that mediate extracellular communication. Viruses have the capacity to hijack and modify the biogenesis machinery of EVs for their own benefit. The present work provides proteomic results (2D electrophoresis) that show the regulation of the expression of proteins involved in autophagy, oxidative stress, and exosome biogenesis in HUVECs infected with ZIKV. We confirmed that Alix and CD9 proteins were downregulated following the infection. Additionally, EVs isolated from infected cells showed the expression of Alix, and CD9 was increased in contrast to the mock condition. Interestingly, nanoparticle tracking and cryo-microscopy assays revealed that these EVs showed an increase in the quantity and size of ZIKV infection to differences in mock conditions. Furthermore, EVs isolated from infected cells showed infectivity, and both RNA and viral proteins were detected. Finally, our cryo-microscopy analysis revealed that the viral infection promoted morphological changes in these extracellular vesicles to identify vesicles with double and triple vesicles and electrodense and double membranes. In conclusion, our data suggest that ZIKV infection can modulate cellular factors involved in the formation and morphology of EVs in HUVECs. Furthermore, these EVs carry viral elements that may contribute to the dissemination of infection. Future studies aimed at the proteomic and lipidomic composition analyses of these EVs are needed to understand the biological implications in vertical infection.

Flaviviridae is a family of viruses that are mainly transmitted by mosquito vectors of the genus Aedes, which cause febrile illnesses and, in severe cases, haemorrhagic or neurodegenerative conditions. Over time, these viruses have been reported as emerging pathogens, leading to epidemic outbreaks in various regions worldwide. Additionally, climate change has facilitated the migration of these vectors to regions where they were not previously found. Unfortunately, there are currently no effective treatments or vaccines to prevent or combat Orthoflavivirus infections. Consequently, a deeper understanding of the viral biology and the human host immune response is crucial for advancing the development of therapeutic targets. Amongst the molecules involved in the innate immune response to viral infections are antimicrobial peptides (AMPs), which have been studied for decades. However, their role in Orthoflavivirus infections remains poorly understood. Several researchers have proposed the stimulation or exogenous administration of AMPs during various viral infections, highlighting these molecules as potential innovative therapeutic targets. This study compiles current knowledge on AMPs with a specific focus on Orthoflavivirus infections, emphasizing the importance of these promising therapeutic approaches.