Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cell host & microbe, 2018-11, Vol.24 (5), p.731-742.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Cross-reactive DENV antibodies enhance ZIKV infection in human Hofbauer cells•Enhanced ZIKV infection in mid-gestation explants is IgG subclass dependent•ZIKV immune complexes target Hofbauer cells within the villous stroma 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.