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. Graphical abstract Highlights • 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 genes Biological Sciences; Virology; Omics; Transcriptomics
【저자키워드】 Virology, transcriptomics, omics, Biological sciences, 【초록키워드】 SARS-CoV-2, coronavirus, Molecular biology, innate immune response, SARS-CoV, IL-6, knowledge, Infection, interferon, inhibition, NF-kB, Disease progression, Protein, viral replication, RNA sequencing, epithelial cells, Hsp90, virus infection, inhibitor, expression, Calu-3, human cell lines, Analysis, Heat shock, host responses, Biological, target gene, reduction, acute respiratory syndrome, Abstract, infected cells, interferon regulatory factor, pro-inflammatory cytokine, gene expression profile, infected cell, transcriptional activity, nuclear, primary human airway, Genes, suggested, upregulated, epithelial cell line, were expressed, elicited, subset, Temporal, impair, human cell line, pro-inflammatory gene, 【제목키워드】 COVID-19, SARS-CoV-2, therapy, Hsp90, identify, human cell line,