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Journal articles

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, * 
* Corresponding author
1 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
UP11 - Université Paris-Sud - Paris 11 : U9196, IGR - Institut Gustave Roussy : U9196, CNRS - Centre National de la Recherche Scientifique : UMR9196
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
Abstract : 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.
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Julian Buchrieser, Severine S. Degrelle, Thérèse Couderc, Quentin Nevers, Olivier Disson, et al.. IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise. Science, American Association for the Advancement of Science (AAAS), 2019, 365 (6449), pp.176-180. ⟨10.1126/science.aaw7733⟩. ⟨pasteur-02454300⟩

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