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

Cell Host Microbe. 2018 Nov 14;24(5):731-742.e6. doi: 10.1016/j.chom.2018.10.008.


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.

Keywords: Zika virus; antibody-dependent enhancement; cross-reactive antibodies; dengue virus; placental macrophages; type I interferon; vertical transmission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • Antibody-Dependent Enhancement / immunology*
  • Chorionic Villi
  • Cross Reactions / immunology*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dengue / immunology*
  • Dengue Virus / immunology*
  • Female
  • Gene Expression
  • Humans
  • Immunoglobulin G / immunology
  • Infectious Disease Transmission, Vertical
  • Interferon Type I / genetics
  • Interferon Type I / metabolism
  • Macrophages / immunology*
  • Macrophages / virology
  • Placenta / immunology*
  • Pregnancy
  • Virus Internalization
  • Zika Virus
  • Zika Virus Infection / immunology*


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines
  • Immunoglobulin G
  • Interferon Type I