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Necroptosis does not drive disease pathogenesis in a mouse infective model of SARS-CoV-2 in vivo

by Sheerin, Dylan , Doerflinger, Marcel , M. Bader, Stefanie , Mackiewicz, Liana , Bhandari, Reet , Georgy, Smitha Rose , Cooney, James P. , Allison, Cody C. , Pellegrini, Marc , Dayton, Merle , Murphy, James M. , Davidson, Kathryn C.

in 13/21 / 13/51 / 631/250/127/1220 / 64/60 / 692/699/255/2514 / Adapter proteins / Antibodies / Apoptosis / Biochemistry / Biomedical and Life Sciences / Cell Biology / Cell Culture / Cell death / COVID-19 / Cytokines / Immunology / Infections / Inflammation / Interferon / Kinases / Lethality / Life Sciences / Lungs / MAP kinase / Medical research / Necroptosis / Pandemics / Pathogenesis / Pathology / Phosphorylation / Severe acute respiratory syndrome coronavirus 2 / Viral infections

2024

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Necroptosis does not drive disease pathogenesis in a mouse infective model of SARS-CoV-2 in vivo

2024

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Necroptosis does not drive disease pathogenesis in a mouse infective model of SARS-CoV-2 in vivo

2024

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Journal Article

Necroptosis does not drive disease pathogenesis in a mouse infective model of SARS-CoV-2 in vivo

Sheerin, Dylan,

Doerflinger, Marcel,

M. Bader, Stefanie,

Mackiewicz, Liana,

Bhandari, Reet,

Georgy, Smitha Rose,

Cooney, James P.,

Allison, Cody C.,

Pellegrini, Marc,

Dayton, Merle,

Murphy, James M.,

Davidson, Kathryn C.

2024

Overview

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.

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Publisher

Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group

Subject

/ 13/51

/ 64/60