tetano
Editor, Senior Moderator
Cell Death Dis
. 2024 Jan 30;15(1):100.
doi: 10.1038/s41419-024-06471-6. Necroptosis does not drive disease pathogenesis in a mouse infective model of SARS-CoV-2 in vivo
Stefanie M Bader[SUP] 1 2 [/SUP], James P Cooney[SUP] 1 2 [/SUP], Reet Bhandari[SUP] 1 2 [/SUP], Liana Mackiewicz[SUP] 1 [/SUP], Merle Dayton[SUP] 1 [/SUP], Dylan Sheerin[SUP] 1 2 [/SUP], Smitha Rose Georgy[SUP] 3 [/SUP], James M Murphy[SUP] 1 2 4 [/SUP], Kathryn C Davidson[SUP] 1 2 [/SUP], Cody C Allison[SUP] 1 [/SUP], Marc Pellegrini[SUP] #[/SUP][SUP] 1 2 [/SUP], Marcel Doerflinger[SUP] #[/SUP][SUP] 5 6 [/SUP]
Affiliations
Necroptosis, a type of lytic cell death executed by the pseudokinase Mixed Lineage Kinase Domain-Like (MLKL) has been implicated in the detrimental inflammation caused by SARS-CoV-2 infection. We minimally and extensively passaged a single clinical SARS-CoV-2 isolate to create models of mild and severe disease in mice allowing us to dissect the role of necroptosis in SARS-CoV-2 disease pathogenesis. We infected wild-type and MLKL-deficient mice and found no significant differences in viral loads or lung pathology. In our model of severe COVID-19, MLKL-deficiency did not alter the host response, ameliorate weight loss, diminish systemic pro-inflammatory cytokines levels, or prevent lethality in aged animals. Our in vivo models indicate that necroptosis is dispensable in the pathogenesis of mild and severe COVID-19.
. 2024 Jan 30;15(1):100.
doi: 10.1038/s41419-024-06471-6. Necroptosis does not drive disease pathogenesis in a mouse infective model of SARS-CoV-2 in vivo
Stefanie M Bader[SUP] 1 2 [/SUP], James P Cooney[SUP] 1 2 [/SUP], Reet Bhandari[SUP] 1 2 [/SUP], Liana Mackiewicz[SUP] 1 [/SUP], Merle Dayton[SUP] 1 [/SUP], Dylan Sheerin[SUP] 1 2 [/SUP], Smitha Rose Georgy[SUP] 3 [/SUP], James M Murphy[SUP] 1 2 4 [/SUP], Kathryn C Davidson[SUP] 1 2 [/SUP], Cody C Allison[SUP] 1 [/SUP], Marc Pellegrini[SUP] #[/SUP][SUP] 1 2 [/SUP], Marcel Doerflinger[SUP] #[/SUP][SUP] 5 6 [/SUP]
Affiliations
- PMID: 38286985
- PMCID: PMC10825138
- DOI: 10.1038/s41419-024-06471-6
Necroptosis, a type of lytic cell death executed by the pseudokinase Mixed Lineage Kinase Domain-Like (MLKL) has been implicated in the detrimental inflammation caused by SARS-CoV-2 infection. We minimally and extensively passaged a single clinical SARS-CoV-2 isolate to create models of mild and severe disease in mice allowing us to dissect the role of necroptosis in SARS-CoV-2 disease pathogenesis. We infected wild-type and MLKL-deficient mice and found no significant differences in viral loads or lung pathology. In our model of severe COVID-19, MLKL-deficiency did not alter the host response, ameliorate weight loss, diminish systemic pro-inflammatory cytokines levels, or prevent lethality in aged animals. Our in vivo models indicate that necroptosis is dispensable in the pathogenesis of mild and severe COVID-19.