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Cell. 2016 May 19;165(5):1081-91. doi: 10.1016/j.cell.2016.05.008. Epub 2016 May 11.

Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.

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  • 1Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • 2Department of Obstetrics and Gynecology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • 3Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • 4Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • 5Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • 6Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Obstetrics and Gynecology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: mysorekari@wudosis.wustl.edu.
  • 7Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: diamond@borcim.wustl.edu.

Abstract

Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1(-/-)) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations.

PMID:
27180225
PMCID:
PMC4874881
[Available on 2017-05-19]
DOI:
10.1016/j.cell.2016.05.008
[PubMed - indexed for MEDLINE]
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