Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris, France.
CNRS-UMR3569, Paris, France.
Science. 2019 Jul 12;365(6449):176-180. doi: 10.1126/science.aaw7733.
Elevated levels of type I interferon (IFN) during pregnancy are associated with intrauterine growth retardation, preterm birth, and fetal demise through mechanisms that are not well understood. A critical step of placental development is the fusion of trophoblast cells into a multinucleated syncytiotrophoblast (ST) layer. Fusion is mediated by syncytins, proteins deriving from ancestral endogenous retroviral envelopes. Using cultures of human trophoblasts or mouse cells, we show that IFN-induced transmembrane proteins (IFITMs), a family of restriction factors blocking the entry step of many viruses, impair ST formation and inhibit syncytin-mediated fusion. Moreover, the IFN inducer polyinosinic:polycytidylic acid promotes fetal resorption and placental abnormalities in wild-type but not in deleted mice. Thus, excessive levels of IFITMs may mediate the pregnancy complications observed during congenital infections and other IFN-induced pathologies.
怀孕期间Ⅰ型干扰素（IFN）水平升高与胎儿生长受限、早产和胎儿死亡有关，但具体机制尚不清楚。胎盘发育的一个关键步骤是滋养细胞融合成多核合胞滋养层（ST）层。融合是由源自祖先内源性逆转录病毒包膜的蛋白——合胞体蛋白（syncytin）介导的。我们使用人滋养层细胞或小鼠细胞培养物表明，干扰素诱导的跨膜蛋白（IFITMs）是一类限制因子，可阻止许多病毒进入宿主细胞的步骤，IFITMs 会损害 ST 的形成并抑制合胞体蛋白介导的融合。此外，干扰素诱导剂聚肌苷酸：聚胞苷酸在野生型小鼠中促进胎儿吸收和胎盘异常，但在缺失型小鼠中则没有。因此，IFITM 的过度表达可能介导了先天性感染和其他 IFN 诱导的病理过程中观察到的妊娠并发症。
