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

Author(s): Bader, SM; Cooney, JP; Bhandari, R; Mackiewicz, L; Dayton, M; Sheerin, D; Georgy, SR; Murphy, JM; Davidson, KC; Allison, CC; Pellegrini, M; Doerflinger, M;
Details: Publication Year 2024-01-30,Volume 15,Issue #1,Page 100
Journal Title: Cell Death & Disease
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.
Publisher: NPG
Research Division(s): Inflammation; Infectious Diseases And Immune Defence
PubMed ID: 38286985
Publisher's Version: https://doi.org/10.1038/s41419-024-06471-6
Open Access at Publisher's Site: https://doi.org/10.1038/s41419-024-06471-6
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-02-29 09:01:47

Last Modified: 2024-02-29 09:09:06