Publication Database

Virus-induced senescence is a driver and therapeutic target in COVID-19 (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Lee, Soyoung

Yu, Yong

Trimpert, Jakob (WE 5)

Benthani, Fahad

Mairhofer, Mario

Richter-Pechanska, Paulina

Wyler, Emanuel

Belenki, Dimitri

Kaltenbrunner, Sabine

Pammer, Maria

Kausche, Lea

Firsching, Theresa C. (WE 12)

Dietert, Kristina (WE 12)

Schotsaert, Michael

Martínez-Romero, Carles

Singh, Gagandeep

Kunz, Séverine

Niemeyer, Daniela

Ghanem, Riad

Salzer, Helmut J. F.

Paar, Christian

Mülleder, Michael

Uccellini, Melissa

Michaelis, Edward G.

Khan, Amjad

Lau, Andrea

Schönlein, Martin

Habringer, Anna

Tomasits, Josef

Adler, Julia M. (WE 5)

Kimeswenger, Susanne

Gruber, Achim D. (WE 12)

Hoetzenecker, Wolfram

Steinkellner, Herta

Purfürst, Bettina

Motz, Reinhard

Di Pierro, Francesco

Lamprecht, Bernd

Osterrieder, Nikolaus (WE 5)

Landthaler, Markus

Drosten, Christian

García-Sastre, Adolfo

Langer, Rupert

Ralser, Markus

Eils, Roland

Reimann, Maurice

Fan, Dorothy N. Y.

Schmitt, Clemens A.

Quelle

Nature : the international journal of science

Bandzählung: 599

Heftzählung: 7884

Seiten: 283 – 289

ISSN: 0028-0836

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/s41586-021-03995-1

DOI: 10.1038/s41586-021-03995-1

Pubmed: 34517409

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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 mediators5-7. 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 tissue1,8,9. 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.