Dengue virus immunity increases Zika virus-induced damage during pregnancy.

Julia A Brown, Gursewak Singh, Joshua A Acklin, Silviana Lee, James E Duehr, Anupa N Chokola, Justin J Frere, Kevin W Hoffman, Gregory A Foster, David Krysztof, Richard Cadagan, Adam R Jacobs, Susan L Stramer, Florian Krammer, Adolfo García-Sastre, Jean K Lim

Immunity, 50(3), 751-762. 19/03/2019

PMID: 30737148


Zika virus (ZIKV) has recently been associated with birth defects and pregnancy loss after maternal infection. Because dengue virus (DENV) and ZIKV co-circulate, understanding the role of antibody-dependent enhancement in the context of pregnancy is critical. Here, we showed that the presence of DENV-specific antibodies in ZIKV-infected pregnant mice significantly increased placental damage, fetal growth restriction, and fetal resorption. This was associated with enhanced viral replication in the placenta that coincided with an increased frequency of infected trophoblasts. ZIKV-infected human placental tissues also showed increased replication in the presence of DENV antibodies, which was reversed by FcγR blocking antibodies. Furthermore, ZIKV-mediated fetal pathogenesis was enhanced in mice in the presence of a DENV-reactive monoclonal antibody, but not in the presence of the LALA variant …