Researchers from the Yale University School of Medicine in New Haven examined the role of type 1 IFNs in limiting or mediating ZIKV disease within a model of congenital infection, observed after ZIKV infection of type I IFN receptor knockout ( ifnar1 −/− ) dams mating with wild-type sires, resulting in fetuses with functional type 1 IFN signaling.
Pregnant dams carried a mixture of fetuses that expressed or did not express IFN-α/β receptor (IFNAR) ( ifnar1+/− and ifnar1 −/− ) within the same uterus. The researchers found that the titer of virus replication was higher in the placenta of ifnar1 −/− than ifnar1 +/− . Only ifnar1 +/− fetuses were resorbed after ZIKV infection during early pregnancy; ifnar1 −/− littermates continued to develop.
IFNAR signaling in the conceptus was found to inhibit development of the placental labyrinth, resulting in abnormal maternal-fetal barrier architecture after ZIKV infection. Exposure of midgestation human chorionic villous explants to type I IFN resulted in altered placental morphology and cytoskeletal rearrangements within the villous core; this was not seen with exposure to type III IFN.
The results implicate type I IFNs as a possible mediator of pregnancy complications, including spontaneous abortions and growth restriction, in the context of congenital viral infections.
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