Zimmerman, Matthew GQuicke, Kendra MO'Neal, Justin TArora, NitinMachiah, DeepaPriyamvada, LalitaKauffman, Robert CRegister, EmeryAdekunle, OluwaseyiSwieboda, DominikaJohnson, Erica LCordes, SarahHaddad, LisaChakraborty, RanaCoyne, Carolyn BWrammert, JensSuthar, Mehul S2021-04-162021-04-162018-111931-31281934-6069https://hdl.handle.net/10161/22581Zika virus (ZIKV), which emerged in regions endemic to dengue virus (DENV), is vertically transmitted and results in adverse pregnancy outcomes. Antibodies to DENV can cross-react with ZIKV, but whether these antibodies influence ZIKV vertical transmission remains unclear. Here, we find that DENV antibodies increase ZIKV infection of placental macrophages (Hofbauer cells [HCs]) from 10% to over 80% and enhance infection of human placental explants. ZIKV-anti-DENV antibody complexes increase viral binding and entry into HCs but also result in blunted type I interferon, pro-inflammatory cytokine, and antiviral responses. Additionally, ZIKV infection of HCs and human placental explants is enhanced in an immunoglobulin G subclass-dependent manner, and targeting FcRn reduces ZIKV replication in human placental explants. Collectively, these findings support a role for pre-existing DENV antibodies in enhancement of ZIKV infection of select placental cell types and indicate that pre-existing immunity to DENV should be considered when addressing ZIKV vertical transmission.Chorionic VilliMacrophagesPlacentaHumansDengue VirusDengueImmunoglobulin GInterferon Type IAntibodies, MonoclonalAntibodies, ViralCytokinesAntibody-Dependent EnhancementCross ReactionsGene ExpressionPregnancyFemaleVirus InternalizationInfectious Disease Transmission, VerticalAntibodies, NeutralizingZika VirusZika Virus InfectionJournal article2021-04-16