Necroptosis Does Not Drive Disease Pathogenesis in a Mouse Infective Model of SARS-CoV-2 in Vivo

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2024 Jan 29

PMID 38286985

Authors

Stefanie M Bader

James P Cooney

Reet Bhandari

Liana Mackiewicz

Merle Dayton

Dylan Sheerin

Smitha Rose Georgy

James M Murphy

Kathryn C Davidson

Cody C Allison

Marc Pellegrini

Marcel Doerflinger

Affiliations

Soon will be listed here.

Abstract

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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