Journal Article

IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise

Donahue, Daniel A., Souquere, Sylvie, Dupressoir, Anne, Buchrieser, Julian, Ruigrok, Katinka, Nevers, Quentin, Perthame, Emeline, Couderc, Thérèse, Heidmann, Thierry, Arroyo, Marlene V., Manet, Caroline, Porrot, Françoise, Disson, Olivier, Hillion, Kenzo-Hugo, Schwartz, Olivier, Degrelle, Séverine A., Fournier, Thierry, Montagutelli, Xavier, Lecuit, Marc

2019

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science,American Association for the Advancement of Science (AAAS)
• Subject: Abnormalities / Animals / Antigens, Differentiation / Antigens, Differentiation - immunology / Apoptosis Regulatory Proteins / Apoptosis Regulatory Proteins - immunology / Cell Fusion / Cytomegalovirus / Endogenous retroviruses / Female / Fetal Death / Fetal Death - etiology / Fetal Resorption / Fetal Resorption - immunology / Fetuses / Gene Products, env / Gene Products, env - immunology / Glycoproteins / Growth rate / Humans / Intellectual Disability / Interferon / Interferon Type I / Interferon Type I - immunology / Intracellular Signaling Peptides and Proteins / Intracellular Signaling Peptides and Proteins - immunology / Life Sciences / Membrane proteins / Mice / Placenta / Poly I-C / Poly I-C - pharmacology / Pre-eclampsia / Pregnancy / Pregnancy complications / Pregnancy Proteins / Pregnancy Proteins - immunology / Premature birth / Prenatal development / Proteins / RNA-Binding Proteins / RNA-Binding Proteins - immunology / Syncytin / Toxoplasmosis / Trophoblasts / Trophoblasts - drug effects / Trophoblasts - immunology