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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Zimmerman, MG; Quicke, KM; O'Neal, JT; Arora, N; Machiah, D; Priyamvada, L; Kauffman, RC; Register, E; Adekunle, O; Swieboda, D; Johnson, EL; Cordes, S; Haddad, L; Chakraborty, R; Coyne, CB; Wrammert, J; Suthar, MS

Published Date

  • November 14, 2018

Published In

Volume / Issue

  • 24 / 5

Start / End Page

  • 731 - 742.e6

PubMed ID

  • 30439342

Pubmed Central ID

  • 30439342

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2018.10.008

Language

  • eng

Conference Location

  • United States