Uncovering a unique pathogenic mechanism of SARS-CoV-2 omicron variant: selective induction of cellular senescence
Franziska Hornung, Nilay Köse-Vogel, Claude Jourdan Le Saux, Antje Häder, Lea Herrmann, Luise Schulz, Lukáš Radosa, Thurid Lauf, T. Sandhaus, Patrick Samson, Torsten Doenst, Daniel Wittschieber, Gita Mall, Bettina Löffler, Stefanie Deinhardt‐Emmer
Abstract
BACKGROUND: SARS-CoV-2 variants are constantly emerging with a variety of changes in the conformation of the spike protein, resulting in alterations of virus entry mechanisms. Solely omicron variants use the endosomal clathrin-mediated entry. Here, we investigate the influence of defined altered spike formations to study their impact on premature cellular senescence. METHODS: lung slices. We confirmed cellular senescence in human lungs of COVID-19 patients. Hence, global gene expression patterns of infected human primary alveolar epithelial cells were identified via mRNA sequencing. RESULTS: lungs. Additionally, an upregulated senescence-associated secretory phenotype (SASP) was detected. Transcriptomic data indicate an increased gene expression of p16, and p38 in omicron-infected lung cells. CONCLUSIONS: Significant changes due to different SARS-CoV-2 infections in human primary alveolar epithelial cells with an overall impact on premature aging could be identified. A substantially different cellular response with an upregulation of cell cycle, inflammation- and integrin-associated pathways in omicron infected cells indicates premature cellular senescence.