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 syncytio...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2019-07, Vol.365 (6449), p.176-180
Main Authors: Buchrieser, Julian, Degrelle, Séverine A, Couderc, Thérèse, Nevers, Quentin, Disson, Olivier, Manet, Caroline, Donahue, Daniel A, Porrot, Françoise, Hillion, Kenzo-Hugo, Perthame, Emeline, Arroyo, Marlene V, Souquere, Sylvie, Ruigrok, Katinka, Dupressoir, Anne, Heidmann, Thierry, Montagutelli, Xavier, Fournier, Thierry, Lecuit, Marc, Schwartz, Olivier
Format: Article
Language:English
Subjects:
Abnormalities
Animals
Antigens, Differentiation - immunology
Apoptosis Regulatory Proteins - immunology
Cell Fusion
Complications
Cytomegalovirus
Endogenous retroviruses
Female
Fetal Death - etiology
Fetal resorption
Fetal Resorption - immunology
Fetuses
Gene Products, env - immunology
Glycoproteins
Growth rate
Human health and pathology
Humans
Immunology
Infections
Intellectual Disability
Interferon
Interferon Type I - immunology
Intracellular Signaling Peptides and Proteins - immunology
Life Sciences
Membrane proteins
Mice
Microbiology and Parasitology
Placenta
Poly I-C - pharmacology
Pre-eclampsia
Pregnancy
Pregnancy complications
Pregnancy Proteins - immunology
Premature birth
Prenatal development
Proteins
RNA-Binding Proteins - immunology
Syncytin
Toxoplasmosis
Trophoblasts
Trophoblasts - drug effects
Trophoblasts - immunology
Virology
Viruses
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aaw7733