[PDF][PDF] Cross-reactive dengue virus antibodies augment Zika virus infection of human placental macrophages

MG Zimmerman, KM Quicke, JT O'Neal, N Arora… - Cell host & …, 2018 - cell.com
MG Zimmerman, KM Quicke, JT O'Neal, N Arora, D Machiah, L Priyamvada, RC Kauffman…
Cell host & microbe, 2018cell.com
Zika 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 …
Summary
Zika 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.
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