Blocking cell death limits lung damage by influenza

On page 835, Gautam etai? show that by inhibiting a cell-death response called necroptosis - an important innate antiviral strategy - the strength of the inflammatory response in an animal model of severe influenza infection is reduced, substantially reducing mortality. Daily injections of UH15-38 w...

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Bibliographic Details
Published inNature (London) Vol. 628; no. 8009; pp. 726 - 727
Main Authors Gupta, Nishma, Silke, John
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group 25.04.2024
Subjects
Animal models
Apoptosis
Cell death
Coronaviruses
Cytokine storm
Infections
Inflammation
Inflammatory response
Influenza
Inhibitors
Kinases
Laboratory animals
Medical research
Medical treatment
Mortality
Necroptosis
Pandemics
Proteins
Respiratory diseases
Toxicity
Viral infections
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Summary:On page 835, Gautam etai? show that by inhibiting a cell-death response called necroptosis - an important innate antiviral strategy - the strength of the inflammatory response in an animal model of severe influenza infection is reduced, substantially reducing mortality. Daily injections of UH15-38 were well tolerated by mice, with no obvious indications of toxicity and, crucially, the inhibitor was highly effective in reducing mortality in models of influenza infection. [...]UH15-38 didn't increase the survival of infected mice that lack RIPK3 or MLKL, indicating that the effect of the inhibitor is due to on-target activity. Consistent with the effects of UH15-38 and the potential importance for disease treatment using UH15-38, these cells express all of the required necroptotic machinery and, on infection, MLKL becomes phosphorylated, a process that can be blocked by UH15-38.
ISSN:0028-0836
1476-4687
DOI:10.1038/d41586-024-00910-2