IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise

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

doi:10.1126/science.aaw7733

IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise

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

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104 Citations (Scopus)

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.

Original language	English
Pages (from-to)	176-180
Number of pages	5
Journal	Science
Volume	365
Issue number	6449
DOIs	https://doi.org/10.1126/science.aaw7733
Publication status	Published - 1 Jan 2019

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Buchrieser, J., Degrelle, S. A., Couderc, T., Nevers, Q., Disson, O., Manet, C., Donahue, D. A., Porrot, F., Hillion, K. H., Perthame, E., Arroyo, M. V., Souquere, S., Ruigrok, K., Dupressoir, A., Heidmann, T., Montagutelli, X., Fournier, T., Lecuit, M., & Schwartz, O. (2019). IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise. Science, 365(6449), 176-180. https://doi.org/10.1126/science.aaw7733

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title = "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.",

author = "Julian Buchrieser and Degrelle, {S{\'e}verine A.} and Th{\'e}r{\`e}se Couderc and Quentin Nevers and Olivier Disson and Caroline Manet and Donahue, {Daniel A.} and Fran{\c c}oise Porrot and Hillion, {Kenzo Hugo} and Emeline Perthame and Arroyo, {Marlene V.} and Sylvie Souquere and Katinka Ruigrok and Anne Dupressoir and Thierry Heidmann and Xavier Montagutelli and Thierry Fournier and Marc Lecuit and Olivier Schwartz",

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Buchrieser, J, Degrelle, SA, Couderc, T, Nevers, Q, Disson, O, Manet, C, Donahue, DA, Porrot, F, Hillion, KH, Perthame, E, Arroyo, MV, Souquere, S, Ruigrok, K, Dupressoir, A, Heidmann, T, Montagutelli, X, Fournier, T, Lecuit, M & Schwartz, O 2019, 'IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise', Science, vol. 365, no. 6449, pp. 176-180. https://doi.org/10.1126/science.aaw7733

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T1 - IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise

AU - Buchrieser, Julian

AU - Degrelle, Séverine A.

AU - Couderc, Thérèse

AU - Nevers, Quentin

AU - Disson, Olivier

AU - Manet, Caroline

AU - Donahue, Daniel A.

AU - Porrot, Françoise

AU - Hillion, Kenzo Hugo

AU - Perthame, Emeline

AU - Arroyo, Marlene V.

AU - Souquere, Sylvie

AU - Ruigrok, Katinka

AU - Dupressoir, Anne

AU - Heidmann, Thierry

AU - Montagutelli, Xavier

AU - Fournier, Thierry

AU - Lecuit, Marc

AU - Schwartz, Olivier

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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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SN - 0036-8075

VL - 365

SP - 176

EP - 180

JO - Science

JF - Science

IS - 6449

ER -

IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise

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