Intrauterine Zika virus infection of pregnant immunocompetent mice models transplacental transmission and adverse perinatal outcomes

Meghan S. Vermillion, Jun Lei, Yahya Shabi, Victoria K. Baxter, Nathan P. Crilly, Michael McLane, Diane E. Griffin, Andrew Pekosz, Sabra L. Klein, Irina Burd

Research output: Research - peer-reviewArticle

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 IFNb 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.

LanguageEnglish (US)
Article number14575
JournalNature Communications
Volume8
DOIs
StatePublished - Feb 21 2017

Fingerprint

Zika Virus Infection
Zika Virus
viruses
infectious diseases
mice
Viruses
Placenta
inoculation
Brain
Infection
brain
causes
Fetal Viability
Asian Americans
Viral Antigens
Trophoblasts
Microglia
Immune System
Fetus
Stem Cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Intrauterine Zika virus infection of pregnant immunocompetent mice models transplacental transmission and adverse perinatal outcomes. / Vermillion, Meghan S.; Lei, Jun; Shabi, Yahya; Baxter, Victoria K.; Crilly, Nathan P.; McLane, Michael; Griffin, Diane E.; Pekosz, Andrew; Klein, Sabra L.; Burd, Irina.

In: Nature Communications, Vol. 8, 14575, 21.02.2017.

Research output: Research - peer-reviewArticle

Vermillion MS, Lei J, Shabi Y, Baxter VK, Crilly NP, McLane M et al. Intrauterine Zika virus infection of pregnant immunocompetent mice models transplacental transmission and adverse perinatal outcomes. Nature Communications. 2017 Feb 21;8. 14575. Available from, DOI: 10.1038/ncomms14575
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