Mrs
Annika Dohme
(Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany)
Background: SARS-CoV-2 infections can result in imbalanced immune responses facilitating inflammations in severe COVID-19 cases. Glucocorticoids (GCs), such as dexamethasone, have become a standard therapy for controlling the inflammatory response. The immunosuppressive features of GCs resulted in controversies about whether GC treatment should be implemented during virus infections. Glucocorticoid receptor activation (GRA) induces an immunosuppressive state but also shows induction of autophagy and enhancement of metabolism.
Goal: As SARS-CoV-2 limits autophagy and modulates metabolism, we hypothesize direct modulations of SARS-CoV-2 to GR signaling.
Results: We show that SARS-CoV-2 infection causes an accumulation of key metabolites whereas GC-treated Calu-3 human lung cells show the opposite effect. Some GR target proteins are upregulated upon SARS-CoV-2 infection. Despite endogenous GRA, we detect COVID-19 prototypic pro-inflammatory cytokine secretion upon SARS-CoV-2 infection. GC co-treatment during infection leads to a significant reduction of cytokine secretion with comparable or even enhanced viral replication in Calu-3 cells.
Conclusion: SARS-CoV-2 infection is modulating GR signaling and immunometabolism likely to promote its own propagation. Future investigations aim at characterizing the exact virus-GR signaling host protein interactions to identify specific host targets for the development of combined antiviral/anti-inflammatory therapies.
Keywords
SARS-CoV-2, Glucocorticoid Receptor, Immunity, Inflammasome, Autophagy
| Registration-ID code |
ZOO23-496
|
| Junior Scientist Status |
Yes, I am a Junior Scientist.
|
| Professional Status of the Speaker |
PhD Student
|
Mrs
Annika Dohme
(Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany)
Mr
Jackson Emanuel
(Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany)
Mr
Thomas Bajaj
(Department of Psychiatry and Psychotherapy, University of Bonn, Medical Faculty, Bonn, Germany)
Dr
Iván Nombela Díaz
(Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany)
Mrs
Julia M. Adler
(Institute of Virology, Freie Universität Berlin, Berlin, Germany)
Dr
Frederik Dethloff
(Max Planck Institute for Biology of Ageing, Cologne, Germany)
Dr
Emanuel Wyler
(Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany)
Dr
Jan Papies
(Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany)
Mr
Nicolas Heinemann
(Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany)
Prof.
Markus Landthaler
(Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; IRI Life Sciences, Institut für Biologie, Humboldt-Universität zu Berlin, Berlin, Germany)
Dr
Patrick Giavalisco
(Max Planck Institute for Biology of Ageing, Cologne, Germany)
Prof.
Christian Drosten
(Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany; German Center for Infection Research (DZIF), partner site Charité, Berlin, Germany)
Dr
Jakob Trimpert
(Institute of Virology, Freie Universität Berlin, Berlin, Germany)
Dr
Nils C. Gassen
(Department of Psychiatry and Psychotherapy, University of Bonn, Medical Faculty, Bonn, Germany)
Prof.
Marcel A. Müller
(Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany; German Center for Infection Research (DZIF), partner site Charité, Berlin, Germany)
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