Fetal-intrinsic antiviral mechanisms emerge over the course of gestation

During pregnancy, an unborn child's immune system develops in a way that influences whether a viral infection will be harmless or harmful to both the mother and the fetus. Researchers, using a mouse model of congenital infection with the Oropouche virus (OROV), have discovered that the stage of pregnancy significantly affects a mother's and baby's response to the virus.

Pregnant mice infected early in their pregnancy face a less severe OROV disease compared to those infected in the middle of their gestation. However, the baby's response varies: it experiences more profound pathology if infected early, but less if infected later. This indicates that the fetus's susceptibility to the virus changes over the course of pregnancy.

Late-stage fetal tissues are more effective at limiting the transmission of the virus from mother to baby, leading to less severe pathology. Both placental and fetal tissues are able to clear the virus's RNA throughout the infection, irrespective of the gestational stage. The inability to clear the virus's RNA is linked to severe fetal pathology.

Additionally, the study reveals a distinct regional vulnerability to OROV infection at the early gestation implantation sites along the maternal-fetal interface. There is also evidence of placental-independent vertical transmission, where the virus can spread directly from the mother's highly infected uterus to her fetus.

The study uncovers an unexpected mechanism where type I interferon signaling plays a crucial role in inter-fetal immune communication. This helps restrict both vertical transmission and pathology of the virus in the fetus. In summary, these findings highlight the fetus as an active participant in antiviral defense and unveil previously unknown mechanisms through which fetal-intrinsic antiviral immune responses can limit congenital viral infection and disease.