| Literature DB >> 30737148 |
Julia A Brown1, Gursewak Singh2, Joshua A Acklin1, Silviana Lee2, James E Duehr1, Anupa N Chokola1, Justin J Frere2, Kevin W Hoffman1, Gregory A Foster3, David Krysztof3, Richard Cadagan4, Adam R Jacobs5, Susan L Stramer3, Florian Krammer2, Adolfo García-Sastre6, Jean K Lim7.
Abstract
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, indicating a dependence on FcγR engagement. Our data suggest a possible mechanism for the recent increase in severe pregnancy outcomes after ZIKV infection in DENV-endemic areas.Entities:
Keywords: Zika virus; antibodies; antibody-dependent enhancement; dengue virus; flavivirus; pathogenesis; placenta; pregnancy; trophoblasts
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Year: 2019 PMID： 30737148 PMCID： PMC6947917 DOI： 10.1016/j.immuni.2019.01.005
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745