title: Intrauterine Zika virus infection of pregnant immunocompetent mice models transplacental transmission and adverse perinatal outcomes.
abstract: Zika virus (ZIKV) crosses the placenta and causes congenital disease. Here we develop an animal model utilizing direct ZIKV inoculation into the uterine wall of pregnant, immunocompetent mice to evaluate transplacental transmission. Intrauterine inoculation at embryonic day (E) 10, but not E14, with African, Asian or American strains of ZIKV reduces fetal viability and increases infection of placental and fetal tissues. ZIKV inoculation at E10 causes placental inflammation, placental dysfunction and reduces neonatal brain cortical thickness, which is associated with increased activation of microglia. Viral antigen localizes in trophoblast and endothelial cells in the placenta, and endothelial, microglial and neural progenitor cells in the fetal brain. ZIKV infection of the placenta increases production of IFNβ and expression of IFN-stimulated genes 48 h after infection. This mouse model provides a platform for identifying factors at the maternal-fetal interface that contribute to adverse perinatal outcomes in a host with an intact immune system.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.|Department of Molecular and Comparative Pathobiology, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Meghan S
authors.initials: MS
authors.lastname: Vermillion
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Lei
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Shabi
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.|Department of Molecular and Comparative Pathobiology, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Baxter
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Crilly
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: McLane
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Griffin
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pekosz
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: Sabra L
authors.initials: SL
authors.lastname: Klein
authors.affiliation: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Burd
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D051379:Mice; D010920:Placenta / Q000821:virology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D011256:Pregnancy Outcome; D014599:Uterus / Q000821:virology*; D014709:Vero Cells; D000071244:Zika Virus / Q000502:physiology*; D000071243:Zika Virus Infection / Q000635:transmission / Q000821:virology*