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

Cell. 2016 May 19;165(5):1081-1091. doi: 10.1016/j.cell.2016.05.008. Epub 2016 May 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Brain / embryology
  • Brain / pathology
  • Brain / virology
  • Disease Models, Animal*
  • Female
  • Fetal Diseases / pathology
  • Fetal Diseases / virology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Placenta Diseases / pathology
  • Placenta Diseases / virology*
  • Pregnancy
  • Pregnancy Complications, Infectious / pathology
  • Pregnancy Complications, Infectious / virology*
  • RNA, Viral / isolation & purification
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / metabolism
  • Zika Virus / physiology*
  • Zika Virus Infection / pathology*
  • Zika Virus Infection / virology

Substances

  • Ifnar1 protein, mouse
  • RNA, Viral
  • Receptor, Interferon alpha-beta