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

2018; Cell Press; Volume: 24; Issue: 5 Linguagem: Inglês

10.1016/j.chom.2018.10.008

1934-6069

Matthew G. Zimmerman, Kendra M. Quicke, Justin T. O’Neal, Nitin Arora, Deepa Machiah, Lalita Priyamvada, Robert C. Kauffman, Emery T. Register, Oluwaseyi Adekunle, Dominika Swieboda, Erica L. Johnson, Sarah Cordes, Lisa B. Haddad, Rana Chakraborty, Carolyn B. Coyne, Jens Wrammert, Mehul S. Suthar,

Virology and Viral Diseases

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.