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ripk, iav, mice, infection, article, dose, pubmed, cell, pfu, google, scholar, apoptosis, necroptosis, protection, cas, mlkl, viral, influenza, virus, vivo, death, kinase, doses, challenge, fadd, survival, medium, low, activity, cells, role, nature, shown, protective, infected, fig, central, activation, loss, inflammasome, mechanism, ripkdeficient, susceptibility, controls, littermates, high, bodyweight, function, data, independent,

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nature portfolio privacy policy age-matched ripk3 kd-kik51a/k51a nature 471 nature advertising ripk3 kd-kik51a/k51a social media embryo development human-origin laboratory strain caspase-8-mediated cell-extrinsic apoptosis research foundation flanders reprints age-matched ripk3−/−fadd−/− dko fwo research grants excessive ripk3/mlkl-mediated necroptosis adapter-inducing interferon-β virus-induced cell death inflammasome-independent il-1α madin-darby canine kidney mlkl post-translational modifications author information authors cell-autonomous defense mechanism cell death-independent mechanism 5 mg/kg xylazine intraperitoneally ripk3-independent fadd-mediated apoptosis inflammation research fadd-caspase-8-cflipl complex acute lung injury viral mitochondria-localized inhibitor cell death molecules consecutive mlkl-mediated necroptosis mlkl-deficient mice displayed mlkl-deficient mice challenged challenged mlkl-deficient mice research induce nf-kb activation negative-stranded rna viruses permissions ripk3 platform activity-dependent full size image tom vanden berghe author correspondence original author programmed cell death cell death mechanism ripk3 platform-mediated apoptosis anti-influenza virus immunity fadd-caspase-8 apoptotic axis cell death dis

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         headline:Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL
         description:RIPK3 was reported to play an important role in the protection against influenza A virus (IAV) in vivo. Here we show that the requirement of RIPK3 for protection against IAV infection in vivo is only apparent within a limited dose range of IAV challenge. We found that this protective outcome is independent from RIPK3 kinase activity and from MLKL. This shows that platform function of RIPK3 rather than its kinase activity is required for protection, suggesting that a RIPK3 function independent of necroptosis is implicated. In line with this finding, we show that FADD-dependent apoptosis has a crucial additional effect in protection against IAV infection. Altogether, we show that RIPK3 contributes to protection against IAV in a narrow challenge dose range by a mechanism that is independent of its kinase activity and its capacity to induce necroptosis.
         datePublished:2021-05-11T00:00:00Z
         dateModified:2021-05-11T00:00:00Z
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      headline:Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL
      description:RIPK3 was reported to play an important role in the protection against influenza A virus (IAV) in vivo. Here we show that the requirement of RIPK3 for protection against IAV infection in vivo is only apparent within a limited dose range of IAV challenge. We found that this protective outcome is independent from RIPK3 kinase activity and from MLKL. This shows that platform function of RIPK3 rather than its kinase activity is required for protection, suggesting that a RIPK3 function independent of necroptosis is implicated. In line with this finding, we show that FADD-dependent apoptosis has a crucial additional effect in protection against IAV infection. Altogether, we show that RIPK3 contributes to protection against IAV in a narrow challenge dose range by a mechanism that is independent of its kinase activity and its capacity to induce necroptosis.
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      name:VIB-UGent Center for Inflammation Research, Ghent, Belgium
      name:Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
      name:Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
      name:Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
      name:VIB-UGent Center for Medical Biotechnology, Ghent, Belgium
      name:Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium
      name:VIB-UGent Center for Inflammation Research, Ghent, Belgium
      name:Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
      name:VIB-UGent Center for Inflammation Research, Ghent, Belgium
      name:Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
      name:VIB-UGent Center for Inflammation Research, Ghent, Belgium
      name:Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium

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