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000278563 1001_ $$00000-0001-9192-5866$$aKrchlikova, Veronika$$b0
000278563 245__ $$aInhibition of placental trophoblast fusion by guanylate-binding protein 5.
000278563 260__ $$aWashington, DC [u.a.]$$bAssoc.$$c2025
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000278563 520__ $$aSyncytin-1 and Syncytin-2 are envelope glycoproteins encoded by human endogenous retroviruses that have been exapted for the fusion of cytotrophoblast cells into syncytiotrophoblasts during placental development. Pregnancy complications like preeclampsia are associated with altered expression of interferon-stimulated genes, including guanylate-binding protein 5 (GBP5). Here, we show that misdirected antiviral activity of GBP5 impairs processing and activation of Syncytin-1. In contrast, the proteolytic activation of Syncytin-2 is not affected by GBP5, and its fusogenic activity is only modestly reduced. Mechanistic analyses revealed that Syncytin-1 is mainly cleaved by the GBP5 target furin, whereas Syncytin-2 is also efficiently processed by the proprotein convertase subtilisin/kexin type 7 (PCSK7) and thus resistant to GBP5-mediated restriction. Mutational analyses mapped PCSK7 processing of Syncytin-2 to a leucine residue upstream of the polybasic cleavage site. In summary, we identified an innate immune mechanism that impairs the activity of a co-opted endogenous retroviral envelope protein during pregnancy and may potentially contribute to the pathogenesis of pregnancy disorders.
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000278563 650_7 $$2NLM Chemicals$$aPregnancy Proteins
000278563 650_7 $$0EC 3.6.1.-$$2NLM Chemicals$$aGTP-Binding Proteins
000278563 650_7 $$0EC 3.4.21.75$$2NLM Chemicals$$aFurin
000278563 650_7 $$2NLM Chemicals$$aGene Products, env
000278563 650_7 $$2NLM Chemicals$$asyncytin
000278563 650_2 $$2MeSH$$aHumans
000278563 650_2 $$2MeSH$$aTrophoblasts: metabolism
000278563 650_2 $$2MeSH$$aTrophoblasts: cytology
000278563 650_2 $$2MeSH$$aFemale
000278563 650_2 $$2MeSH$$aPregnancy
000278563 650_2 $$2MeSH$$aPregnancy Proteins: metabolism
000278563 650_2 $$2MeSH$$aPregnancy Proteins: genetics
000278563 650_2 $$2MeSH$$aGTP-Binding Proteins: metabolism
000278563 650_2 $$2MeSH$$aGTP-Binding Proteins: genetics
000278563 650_2 $$2MeSH$$aFurin: metabolism
000278563 650_2 $$2MeSH$$aPlacenta: metabolism
000278563 650_2 $$2MeSH$$aPlacenta: cytology
000278563 650_2 $$2MeSH$$aGene Products, env: metabolism
000278563 650_2 $$2MeSH$$aGene Products, env: genetics
000278563 650_2 $$2MeSH$$aCell Fusion
000278563 7001_ $$00000-0002-3595-7107$$aBraun, Elisabeth$$b1
000278563 7001_ $$aWeiss, Johanna$$b2
000278563 7001_ $$00000-0001-8708-606X$$aStafl, Krystof$$b3
000278563 7001_ $$00009-0004-6345-906X$$aJech, Lukas$$b4
000278563 7001_ $$00000-0002-4591-0513$$aBadarinarayan, Smitha Srinivasachar$$b5
000278563 7001_ $$00000-0001-9630-7100$$aLotke, Rishikesh$$b6
000278563 7001_ $$00000-0003-0627-2560$$aTravnicek, Martin$$b7
000278563 7001_ $$aBaur, Charlotte$$b8
000278563 7001_ $$00009-0004-9151-2032$$aStark, Paul$$b9
000278563 7001_ $$aHaussmann, Isabell$$b10
000278563 7001_ $$aLu, Yueshuang$$b11
000278563 7001_ $$aPetersen, Moritz$$b12
000278563 7001_ $$aCui, Wen$$b13
000278563 7001_ $$0P:(DE-HGF)0$$aWang, Wei$$b14
000278563 7001_ $$aFäger, Bianca M$$b15
000278563 7001_ $$aReisinger, Hannah$$b16
000278563 7001_ $$00000-0002-2625-5322$$aTokunaga, Kenzo$$b17
000278563 7001_ $$00000-0002-0096-4948$$aCingöz, Oya$$b18
000278563 7001_ $$0P:(DE-2719)9003481$$aSparrer, Konstantin M J$$b19
000278563 7001_ $$00000-0002-7939-289X$$aSalker, Madhuri S$$b20
000278563 7001_ $$aHejnar, Jiri$$b21
000278563 7001_ $$00000-0002-7052-2360$$aKirchhoff, Frank$$b22
000278563 7001_ $$00000-0002-9872-3041$$aTrejbalova, Katerina$$b23
000278563 7001_ $$00000-0001-7665-0040$$aSauter, Daniel$$b24
000278563 773__ $$0PERI:(DE-600)2810933-8$$a10.1126/sciadv.adt5388$$gVol. 11, no. 19, p. eadt5388$$n19$$peadt5388$$tScience advances$$v11$$x2375-2548$$y2025
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