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Immunity. 2019 Jan 30. pii: S1074-7613(19)30028-7. doi: 10.1016/j.immuni.2019.01.005. [Epub ahead of print]

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

Author information

1
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
3
American Red Cross, Gaithersburg, MD, USA.
4
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
5
Department of Obstetrics and Gynecology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
6
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
7
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: jean.lim@mssm.edu.

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.

KEYWORDS:

Zika virus; antibodies; antibody-dependent enhancement; dengue virus; flavivirus; pathogenesis; placenta; pregnancy; trophoblasts

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