Gestational Stage and IFN-λ Signaling Regulate ZIKV Infection In Utero

Brett W Jagger, Jonathan J Miner, Bin Cao, Nitin Arora, Amber M Smith, Attila Kovacs, Indira U Mysorekar, Carolyn B Coyne, Michael S Diamond
Cell Host and Microbe2017
Although Zika virus (ZIKV)-induced congenital dis- ease 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 preg- nancy (E12) caused no apparent fetal disease. In addition, we found that fetuses lacking type III IFN-l signaling had increased ZIKV replication in the placenta and fetus when infected at E12, and reciprocally, treatment of pregnant mice with IFN-l2 reduced ZIKV infection. IFN-l treatment analogously diminished ZIKV infection in human midgestation fetal- and maternal-derived tissue ex- plants. Our data establish a model of gestational stage dependence of ZIKV pathogenesis and IFN-l-mediated immunity at the maternal-fetal interface.
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