Abstract

Although Zika virus (ZIKV)-induced congenital disease occurs more frequently during early stages of pregnancy, its basis remains undefined. Using established type I interferon (IFN)-deficient mouse models of ZIKV transmission in utero, we found that the placenta and fetus were more susceptible to ZIKV infection at earlier gestational stages. Whereas ZIKV infection at embryonic day 6 (E6) resulted in placental insufficiency and fetal demise, infections at midstage (E9) resulted in reduced cranial dimensions, and infection later in pregnancy (E12) caused no apparent fetal disease. In addition, we found that fetuses lacking type III IFN-λ signaling had increased ZIKV replication in the placenta and fetus when infected at E12, and reciprocally, treatment of pregnant mice with IFN-λ2 reduced ZIKV infection. IFN-λ treatment analogously diminished ZIKV infection in human midgestation fetal- and maternal-derived tissue explants. Our data establish a model of gestational stage dependence of ZIKV pathogenesis and IFN-λ-mediated immunity at the maternal-fetal interface. Jagger et al. report that severity of Zika virus (ZIKV)-induced adverse fetal outcomes correlates with placentation and gestational stage at the time of infection. IFN-λ signaling in maternal and fetal tissues restricted placental and fetal ZIKV infection. IFN-λ treatment limited ZIKV transmission in pregnant mice and in human midgestation tissues.

Original languageEnglish
Pages (from-to)366-376.e3
JournalCell Host and Microbe
Volume22
Issue number3
DOIs
StatePublished - Sep 13 2017

Keywords

  • Zika virus
  • flavivirus
  • gestational stage
  • host immunity
  • innate immunity
  • interferon lambda
  • pathogenesis
  • pregnancy

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