IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise

Julian Buchrieser (1) , Severine S. Degrelle (2, 3) , Thérèse Couderc (4) , Quentin Nevers (1) , Olivier Disson (4) , Caroline Manet (5) , Daniel A Donahue (1) , Françoise Porrot (1) , Kenzo-Hugo Hillion (6) , Emeline Perthame (6) , Marlene V Arroyo (1, 7) , Sylvie Souquere (8) , Katinka Ruigrok (9) , Anne Dupressoir (10) , Thierry Heidmann (10) , Xavier Montagutelli (5) , Thierry Fournier (2) , Marc Lecuit (4, 11, 12, 13, 14) , Olivier Schwartz (15, 1)

1 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
2 3PHM - UMR-S 1139 - Physiopathologie et pharmacotoxicologie placentaire humaine : Microbiote pré & post natal
3 Inovarion [Paris]
4 Biologie des Infections - Biology of Infection
5 Génétique fonctionnelle de la Souris
6 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
7 HHMI - Howard Hughes Medical Institute [New York]
8 AMMICa - Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse
9 Virologie Structurale - Structural Virology
10 UMR 9196 - Rétrovirus endogènes et éléments rétroïdes des eucaryotes supérieurs
11 UPD5 - Université Paris Descartes - Paris 5
12 CHU Necker - Enfants Malades [AP-HP]
13 Service des Maladies infectieuses et tropicales [CHU Necker]
14 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
15 VRI - Vaccine Research Institute

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.

Domains: Life Sciences [q-bio]; Human health and pathology; Microbiology and Parasitology; Virology; Immunology

Julian Buchrieser, Severine S. Degrelle, Thérèse Couderc, Quentin Nevers, Olivier Disson, et al.. IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise. Science, 2019, 365 (6449), pp.176-180. ⟨10.1126/science.aaw7733⟩. ⟨pasteur-02454300⟩