Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages

Academic Article

Abstract

  • © 2018 Elsevier Inc. 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. Zimmerman et al. find that DENV cross-reactive antibodies enhance ZIKV infection of human placental macrophages and mid-gestation placental explants. ZIKV-anti-DENV antibody complexes increase viral entry but also result in blunted antiviral responses. These studies suggest that pre-existing immunity to DENV should be considered when addressing ZIKV vertical transmission.
  • Authors

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    Digital Object Identifier (doi)

    Author List

  • Zimmerman MG; Quicke KM; O'Neal JT; Arora N; Machiah D; Priyamvada L; Kauffman RC; Register E; Adekunle O; Swieboda D
  • Start Page

  • 731
  • End Page

  • 742.e6
  • Volume

  • 24
  • Issue

  • 5