Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.
Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.
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DOI：
10.1016/j.cell.2016.05.008
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发表时间：
2016-05-19
期刊：
影响因子：
64.5
通讯作者：
Diamond MS
中科院分区：
文献类型：
--
作者：
Miner JJ;Cao B;Govero J;Smith AM;Fernandez E;Cabrera OH;Garber C;Noll M;Klein RS;Noguchi KK;Mysorekar IU;Diamond MS
孕妇感染寨卡病毒（ZIKV）会导致胎儿宫内生长受限、自然流产和小头畸形。在这里，我们描述了与ZIKV的子宫内传播相关的胎盘和胎儿疾病的两种小鼠模型。缺乏I型干扰素信号传导（Ifnar 1 −/−）的雌性小鼠与野生型（WT）雄性小鼠杂交产生了类似于人类胎儿免疫状态的杂合子胎儿。在胚胎第6.5天（E6.5）或E7.5天的母体接种导致胎儿死亡，这与胎盘和胎儿脑的ZIKV感染相关。我们在母体和胎儿胎盘的滋养层内鉴定了ZIKV，这与经胎盘感染途径一致。WT妊娠小鼠中Ifnar 1信号传导的抗体阻断增强了ZIKV经胎盘感染，尽管其不导致胎儿死亡。这些模型将促进ZIKV发病机制、子宫内传播的研究，以及预防先天性畸形的疗法和疫苗的测试。
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.