The authors were interested in the role of antibody-dependent enhancement in the context of pregnancy during co-infection with dengue virus (DENV) and Zika virus (ZIKV). They found that the presence of DENV-specific antibodies in ZIKV-infected pregnant mice significantly increased placental damage, fetal growth restriction and fetal resorption. This was also associated with enhanced viral replication in the placenta that coincided with an increased frequency of infected trophoblasts. ZIKV-infected human placental tissues also demonstrated increased replication in the presence of DENV antibodies, which could be reversed by FcγR blocking antibodies. In addition, 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, suggesting a dependence on FcγR engagement. Therefore this represents a possible mechanism for increases in severe pregnancy outcomes following ZIKV infection in DENV-endemic areas.
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