两项关于寨卡病毒（ZIKV）的不相关研究---一项研究排除了一种关于ZIKV如何可能穿过人胎盘进行传播的观点，而另一项研究利用小鼠模型追踪ZIKV发病过程---于2016年4月5日在线发表在Cell Host & Microbe期刊上，论文标题分别为“Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection”和“A Mouse Model of Zika Virus Pathogenesis”。
美国匹兹堡大学马吉妇科研究所（Magee-Womens Research Institute）主任Yoel Sadovsky说，“滋养层是胎儿抵抗来自母体血液的任何东西的第一道防线，因此人们可能期待滋养层细胞能够抵抗病毒感染。基于我们的研究结果，滋养层天生就具有抵抗ZIKV增殖的能力，不过我们也并不排除这种病毒能够有其他的途径侵入胎儿隔腔（fetal cavity）中。”
作者: ipsvirus 时间: 2016-4-7 21:14 Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection
Avraham Bayer1, 2, 7, Nicholas J. Lennemann3, 7, Yingshi Ouyang1, 2, John C. Bramley3, Stefanie Morosky3, Ernesto Torres De Azeved Marques Jr.4, 5, Sara Cherry6, Yoel Sadovsky1, 2, 3, , , Carolyn B. Coyne1, 2, 3,
Summary
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 (PHTs), 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 suggest 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.
Helen M. Lazear1, Jennifer Govero2, Amber M. Smith2, Derek J. Platt2, Estefania Fernandez2, Jonathan J. Miner2, Michael S. Diamond2, 3, 4, 5,
Summary
The ongoing Zika virus (ZIKV) epidemic and unexpected clinical outcomes, including Guillain-Barré syndrome and birth defects, has brought an urgent need for animal models. We evaluated infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and mice lacking components of the antiviral response. Four- to six-week-old Irf3−/−Irf5−/−Irf7−/− triple knockout mice, which produce little interferon α/β, and mice lacking the interferon receptor (Ifnar1−/−) developed neurological disease and succumbed to ZIKV infection, whereas single Irf3−/−, Irf5−/−, and Mavs−/− knockout mice exhibited no overt illness. Ifnar1−/− mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses. The testes of Ifnar1−/− mice had the highest viral loads, which is relevant to sexual transmission of ZIKV. This model of ZIKV pathogenesis will be valuable for evaluating vaccines and therapeutics as well as understanding disease pathogenesis.
