iScience (Mar 2021)
Transcriptomic profiling of SARS-CoV-2 infected human cell lines identifies HSP90 as target for COVID-19 therapy
- Emanuel Wyler,
- Kirstin Mösbauer,
- Vedran Franke,
- Asija Diag,
- Lina Theresa Gottula,
- Roberto Arsiè,
- Filippos Klironomos,
- David Koppstein,
- Katja Hönzke,
- Salah Ayoub,
- Christopher Buccitelli,
- Karen Hoffmann,
- Anja Richter,
- Ivano Legnini,
- Andranik Ivanov,
- Tommaso Mari,
- Simone Del Giudice,
- Jan Papies,
- Samantha Praktiknjo,
- Thomas F. Meyer,
- Marcel Alexander Müller,
- Daniela Niemeyer,
- Andreas Hocke,
- Matthias Selbach,
- Altuna Akalin,
- Nikolaus Rajewsky,
- Christian Drosten,
- Markus Landthaler
Affiliations
- Emanuel Wyler
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany; Corresponding author
- Kirstin Mösbauer
- Institute of Virology, Charité-Universitätsmedizin Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
- Vedran Franke
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany
- Asija Diag
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany
- Lina Theresa Gottula
- Institute of Virology, Charité-Universitätsmedizin Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
- Roberto Arsiè
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany
- Filippos Klironomos
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany; Department of Pediatrics, Charité – University Hospital Berlin, 13353 Berlin, Germany
- David Koppstein
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany
- Katja Hönzke
- Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité University Medicine, Berlin, Germany
- Salah Ayoub
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany
- Christopher Buccitelli
- Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Strasse 10, 13125 Berlin, Germany
- Karen Hoffmann
- Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité University Medicine, Berlin, Germany
- Anja Richter
- Institute of Virology, Charité-Universitätsmedizin Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
- Ivano Legnini
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany
- Andranik Ivanov
- Core Unit Bioinformatics, Berlin Institute of Health, Charité – University Hospital Berlin, 10117 Berlin, Germany
- Tommaso Mari
- Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Strasse 10, 13125 Berlin, Germany
- Simone Del Giudice
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany
- Jan Papies
- Institute of Virology, Charité-Universitätsmedizin Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
- Samantha Praktiknjo
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany
- Thomas F. Meyer
- Laboratory of Infection Oncology, Institute of Clinical Molecular Biology, UKSH, Christian Albrechts University of Kiel, 24105 Kiel, Germany
- Marcel Alexander Müller
- Institute of Virology, Charité-Universitätsmedizin Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
- Daniela Niemeyer
- Institute of Virology, Charité-Universitätsmedizin Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
- Andreas Hocke
- Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité University Medicine, Berlin, Germany
- Matthias Selbach
- Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Strasse 10, 13125 Berlin, Germany
- Altuna Akalin
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany
- Nikolaus Rajewsky
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany
- Christian Drosten
- Institute of Virology, Charité-Universitätsmedizin Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; Corresponding author
- Markus Landthaler
- Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany; IRI Life Sciences, Institut für Biologie, Humboldt Universität zu Berlin, Philippstraße 13, 10115 Berlin, Germany; Corresponding author
- Journal volume & issue
-
Vol. 24,
no. 3
p. 102151
Abstract
Summary: Detailed knowledge of the molecular biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is crucial for understanding of viral replication, host responses, and disease progression. Here, we report gene expression profiles of three SARS-CoV- and SARS-CoV-2-infected human cell lines. SARS-CoV-2 elicited an approximately two-fold higher stimulation of the innate immune response compared to SARS-CoV in the human epithelial cell line Calu-3, including induction of miRNA-155. Single-cell RNA sequencing of infected cells showed that genes induced by virus infections were broadly upregulated, whereas interferon beta/lambda genes, a pro-inflammatory cytokines such as IL-6, were expressed only in small subsets of infected cells. Temporal analysis suggested that transcriptional activities of interferon regulatory factors precede those of nuclear factor κB. Lastly, we identified heat shock protein 90 (HSP90) as a protein relevant for the infection. Inhibition of the HSP90 activity resulted in a reduction of viral replication and pro-inflammatory cytokine expression in primary human airway epithelial cells.
