Transcriptomic profiling of SARS-CoV-2 infected human cell lines identifies HSP90 as target for COVID-19 therapy

iScience

Kirstin Mösbauer¹  Katja Hönzke²  Asija Diag³  Marcel Alexander Müller³  Salah Ayoub³  Filippos Klironomos³  Christian Drosten³  Emanuel Wyler³  Tommaso Mari³  Lina Theresa Gottula³  Karen Hoffmann³  Samantha Praktiknjo³  David Koppstein³  Markus Landthaler³  Simone Del Giudice⁴  Ivano Legnini⁵  Christopher Buccitelli⁵  Altuna Akalin⁵  Andranik Ivanov⁶  Roberto Arsiè⁶  Thomas F. Meyer⁶  Vedran Franke⁶  Matthias Selbach⁶  Andreas Hocke⁶  Daniela Niemeyer⁷  Anja Richter⁸  Jan Papies⁸  Nikolaus Rajewsky⁸ 

[1] Corresponding author;Department of Pediatrics, Charité – University Hospital Berlin, 13353 Berlin, Germany;Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str 28, 10115 Berlin, Germany;Core Unit Bioinformatics, Berlin Institute of Health, Charité – University Hospital Berlin, 10117 Berlin, Germany;Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité University Medicine, Berlin, Germany;Institute of Virology, Charité-Universitätsmedizin Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany;Laboratory of Infection Oncology, Institute of Clinical Molecular Biology, UKSH, Christian Albrechts University of Kiel, 24105 Kiel, Germany;Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Strasse 10, 13125 Berlin, Germany;

关键词: Biological Sciences;    Virology;    Omics;    Transcriptomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown