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@ARTICLE{Krchlikova:278563,
      author       = {Krchlikova, Veronika and Braun, Elisabeth and Weiss,
                      Johanna and Stafl, Krystof and Jech, Lukas and
                      Badarinarayan, Smitha Srinivasachar and Lotke, Rishikesh and
                      Travnicek, Martin and Baur, Charlotte and Stark, Paul and
                      Haussmann, Isabell and Lu, Yueshuang and Petersen, Moritz
                      and Cui, Wen and Wang, Wei and Fäger, Bianca M and
                      Reisinger, Hannah and Tokunaga, Kenzo and Cingöz, Oya and
                      Sparrer, Konstantin M J and Salker, Madhuri S and Hejnar,
                      Jiri and Kirchhoff, Frank and Trejbalova, Katerina and
                      Sauter, Daniel},
      title        = {{I}nhibition of placental trophoblast fusion by
                      guanylate-binding protein 5.},
      journal      = {Science advances},
      volume       = {11},
      number       = {19},
      issn         = {2375-2548},
      address      = {Washington, DC [u.a.]},
      publisher    = {Assoc.},
      reportid     = {DZNE-2025-00596},
      pages        = {eadt5388},
      year         = {2025},
      abstract     = {Syncytin-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.},
      keywords     = {Humans / Trophoblasts: metabolism / Trophoblasts: cytology
                      / Female / Pregnancy / Pregnancy Proteins: metabolism /
                      Pregnancy Proteins: genetics / GTP-Binding Proteins:
                      metabolism / GTP-Binding Proteins: genetics / Furin:
                      metabolism / Placenta: metabolism / Placenta: cytology /
                      Gene Products, env: metabolism / Gene Products, env:
                      genetics / Cell Fusion / Pregnancy Proteins (NLM Chemicals)
                      / GTP-Binding Proteins (NLM Chemicals) / Furin (NLM
                      Chemicals) / Gene Products, env (NLM Chemicals) / syncytin
                      (NLM Chemicals)},
      cin          = {AG Sparrer},
      ddc          = {500},
      cid          = {I:(DE-2719)1910003},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40333975},
      pmc          = {pmc:PMC12057675},
      doi          = {10.1126/sciadv.adt5388},
      url          = {https://pub.dzne.de/record/278563},
}