Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection.
Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection.
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DOI：
10.1016/j.chom.2016.03.008
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发表时间：
2016-05-11
影响因子：
30.3
通讯作者：
Coyne CB
中科院分区：
文献类型：
--
作者：
Bayer A;Lennemann NJ;Ouyang Y;Bramley JC;Morosky S;Marques ET Jr;Cherry S;Sadovsky Y;Coyne CB
在哺乳动物怀孕期间，胎盘充当母体和胎儿隔室之间的屏障。最近观察到的人类妊娠期间寨卡病毒（ZIKV）感染与胎儿小头畸形和其他异常之间的关联表明，ZIKV可能绕过胎盘到达胎儿。这使我们研究了原代人滋养层细胞（PHT）的ZIKV感染，所述滋养层细胞是胎盘的屏障细胞。我们发现来自足月胎盘的PHT细胞对ZIKV感染是难治的。此外，来自未感染的PHT细胞的培养基保护非胎盘细胞免受ZIKV感染。PHT细胞组成性地释放III型干扰素（IFN）IFNλ1，其以旁分泌和自分泌方式起作用以保护滋养层和非滋养层细胞免受ZIKV感染。我们的数据表明，ZIKV要进入胎儿室，必须避开滋养层来源的IFNλ1和其他滋养层特异性抗病毒因子的限制和/或使用替代策略穿过胎盘屏障。
During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZIKV may bypass the placenta to reach the fetus. This led us to investigate ZIKV infection of primary human trophoblasts (PHT), which are the barrier cells of the placenta. We discovered that PHT cells from full-term placentas are refractory to ZIKV infection. In addition, medium from uninfected PHT cells protects non-placental cells from ZIKV infection. PHT cells constitutively release the type III interferon (IFN) IFNλ1, which functions in both a paracrine and autocrine manner to protect trophoblast and non-trophoblast cells from ZIKV infection. Our data suggests that for ZIKV to access the fetal compartment, it must evade restriction by trophoblast-derived IFNλ1 and other trophoblast-specific antiviral factors and/or use alternative strategies to cross the placental barrier.