IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise - Institut Pasteur Access content directly
Journal Articles Science Year : 2019

IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise

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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Origin : Files produced by the author(s)
Licence : CC BY NC ND - Attribution - NonCommercial - NoDerivatives
Origin : Files produced by the author(s)
Licence : CC BY NC ND - Attribution - NonCommercial - NoDerivatives
Licence : CC BY NC ND - Attribution - NonCommercial - NoDerivatives

Dates and versions

pasteur-02454300 , version 1 (26-03-2024)

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Attribution - NonCommercial

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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, 2019, 365 (6449), pp.176-180. ⟨10.1126/science.aaw7733⟩. ⟨pasteur-02454300⟩
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