title: Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.
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.
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Miner
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Cao
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Govero
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Amber M
authors.initials: AM
authors.lastname: Smith
authors.affiliation: Department 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.
authors.forename: Estefania
authors.initials: E
authors.lastname: Fernandez
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Omar H
authors.initials: OH
authors.lastname: Cabrera
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Charise
authors.initials: C
authors.lastname: Garber
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Noll
authors.affiliation: Department 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.
authors.forename: Robyn S
authors.initials: RS
authors.lastname: Klein
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Noguchi
authors.affiliation: Department 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.
authors.forename: Indira U
authors.initials: IU
authors.lastname: Mysorekar
authors.affiliation: Department 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.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000196:embryology / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000473:pathology / Q000821:virology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010922:Placenta Diseases / Q000473:pathology / Q000821:virology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000473:pathology / Q000821:virology*; D012367:RNA, Viral / Q000302:isolation & purification; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism; D000071244:Zika Virus / Q000502:physiology*; D000071243:Zika Virus Infection / Q000473:pathology* / Q000821:virology
chemical_list: C508032:Ifnar1 protein, mouse; D012367:RNA, Viral; D053633:Receptor, Interferon alpha-beta