| Help | About | Contact Us

Publication : Virus-induced senescence is a driver and therapeutic target in COVID-19.

First Author	Lee S	Year	2021
Journal	Nature	Volume	599
Issue	7884	Pages	283-289
PubMed ID	34517409	Mgi Jnum	J:334872
Mgi Id	MGI:7294121	Doi	10.1038/s41586-021-03995-1
Citation	Lee S, et al. (2021) Virus-induced senescence is a driver and therapeutic target in COVID-19. Nature 599(7884):283-289

abstractText

Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs. (1-4)). Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators(5-7). Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue(1,8,9). Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections.

Your name:
Your email address:
Subject:
Message:	---- Current page: ---- /mousemine/report.do;jsessionid=233136BA7A60FBC2BE1A10CF268CB464?id=74543223&trail=%7C74543223

MouseMine

Publication : Virus-induced senescence is a driver and therapeutic target in COVID-19.

External Links

Expression

Publication --> Expression annotations

Other

48 Authors

3 Bio Entities

0 Expression