Fig. 2: Transplacental trafficking of SARS-CoV-2 ORF8 and activation of fetal immune complement pathways.
From: Mechanistic insights into the impact of prenatal viral infections on maternal and offspring immunity
Following maternal SARS-CoV-2 infection, SARS-CoV-2 may induce fetal immune dysregulation via multiple converging pathways, potentially impacting postnatal neurodevelopment. The SARS-CoV-2 accessory protein ORF8 was detected at the maternal–fetal interface and within fetal compartments. A magnified inset of the interface highlights ORF8 binding to the globular domain of C1qA subunit, initiating classical complement pathway leading to induction of proinflammatory cytokines (IL-17A and IL-17E) and fetal inflammation. Owing to its immunoglobulin-like folding, ORF8 is hypothesized to mimic the Fc region of IgG, facilitating its translocation across the placenta via the neonatal Fc receptor (FcRn).
