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

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Item Type:Article
Title:Transcriptomic profiling of SARS-CoV-2 infected human cell lines identifies HSP90 as target for COVID-19 therapy
Creators Name:Wyler, E. and Mösbauer, K. and Franke, V. and Diag, A. and Gottula, L.T. and Arsiè, R. and Klironomos, F. and Koppstein, D. and Hönzke, K. and Ayoub, S. and Buccitelli, C. and Hoffmann, K. and Richter, A. and Legnini, I. and Ivanov, A. and Mari, T. and Del Giudice, S. and Papies, J. and Praktiknjo, S. and Meyer, T.F. and Müller, M.A. and Niemeyer, D. and Hocke, A. and Selbach, M. and Akalin, A. and Rajewsky, N. and Drosten, C. and Landthaler, M.
Abstract:Detailed knowledge of the molecular biology of 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 an 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.
Source:iScience
ISSN:2589-0042
Publisher:Cell Press
Volume:24
Number:3
Page Range:102151
Date:19 March 2021
Official Publication:https://doi.org/10.1016/j.isci.2021.102151
PubMed:View item in PubMed

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