Fig 3. Proposed mechanism of FcRn-mediated transcytosis of a ZIKV–IgG complex in a chorionic villus.

Illustrated is a chorionic villus that is anchored to the mucosal lining of the uterus (decidua). Through the circulation of the mother, ZIKV bound to maternal cross-reactive flavivirus IgG antibodies is present in the intervillous space. This IgG–virion complex can subsequently cross the syncytiotrophoblasts via FcRn-mediated transcytosis. When ZIKV is transcytosed across this trophoblast layer, it can infect the perivascular-located Hofbauer cells, after which viral progeny can cross the endothelial cell barrier, possibly with help from ZIKV NS1 protein, and reach the fetal circulation. FcRn, neonatal fragment crystallizable receptor; IgG, immunoglobulin G; NS1, nonstructural protein 1; ZIKV, Zika virus.