IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise

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 Ifitm-deleted mice. Thus, excessive levels of IFITMs may mediate the pregnancy complications observed during congenital infections and other IFN-induced pathologies.

Source: ScienceNOW - July 10, 2019 Category: Science Authors: Buchrieser, J., Degrelle, S. A., Couderc, T., Nevers, Q., Disson, O., Manet, C., Donahue, D. A., Porrot, F., Hillion, K.-H., Perthame, E., Arroyo, M. V., Souquere, S., Ruigrok, K., Dupressoir, A., Heidmann, T., Montagutelli, X., Fournier, T., Lecuit, M., Tags: Immunology, Microbiology reports Source Type: news