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3743873 
Journal Article 
Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise 
Miner, JJ; Cao, B; Govero, J; Smith, AM; Fernandez, E; Cabrera, OH; Garber, C; Noll, M; Klein, RS; Noguchi, KK; Mysorekar, IU; Diamond, MS 
2016 
Yes 
Cell
ISSN: 0092-8674
EISSN: 1097-4172 
165 
5 
1081-1091 
English 
27180225 
WOS:000376478200010 
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.