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Publication : Dengue Virus Immunity Increases Zika Virus-Induced Damage during Pregnancy.

First Author  Brown JA Year  2019
Journal  Immunity Volume  50
Issue  3 Pages  751-762.e5
PubMed ID  30737148 Mgi Jnum  J:282449
Mgi Id  MGI:6380959 Doi  10.1016/j.immuni.2019.01.005
Citation  Brown JA, et al. (2019) Dengue Virus Immunity Increases Zika Virus-Induced Damage during Pregnancy. Immunity 50(3):751-762.e5
abstractText  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 FcgammaR 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, indicating a dependence on FcgammaR engagement. Our data suggest a possible mechanism for the recent increase in severe pregnancy outcomes after ZIKV infection in DENV-endemic areas.
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