摘要：SummaryDetailed 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.Graphical abstractDisplay OmittedHighlights•Transcriptomic landscape of human cell lines infected with SARS-CoV or SARS-CoV-2•Stronger innate immune response to SARS-CoV-2 and induction of miR-155•Transcription of interferon gene is transient and followed by NF-kB target genes•Hsp90 inhibitors impair viral replication and induction of pro-inflammatory genesBiological Sciences; Virology; Omics; Transcriptomics
