Comparative transcriptomic analyzes of human lung epithelial cells infected with wild-type SARS-CoV-2 and its variant with a 12-bp missing in the E gene

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused a global outbreak of coronavirus disease 2019 (COVID-19) pandemic. To elucidate the mechanism of SARS-CoV-2 replication and immunogenicity, we performed a comparative transcriptome profile of mRNA and long non-coding RNAs (lncRNAs) in human lung epithelial cells infected with the SARS-CoV-2 wild-type strain (8X) and the variant with a 12-bp deletion in the E gene (F8). In total, 3,966 differentially expressed genes (DEGs) and 110 differentially expressed lncRNA (DE-lncRNA) candidates were identified. Of these, 94 DEGs and 32 DE-lncRNAs were found between samples infected with F8 and 8X. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzes revealed that pathways such as the TNF signaling pathway and viral protein interaction with cytokine and cytokine receptor were involved. Furthermore, we constructed a lncRNA-protein-coding gene co-expression interaction network. The KEGG analysis of the co-expressed genes showed that these differentially expressed lncRNAs were enriched in pathways related to the immune response, which might explain the different replication and immunogenicity properties of the 8X and F8 strains. These results provide a useful resource for studying the pathogenesis of SARS-CoV-2 variants.

Transcriptional Profiling of SARS-CoV-2-Infected Calu-3 Cells Reveals Immune-Related Signaling Pathways

“…Our results are in line with other transcriptome studies conducted in SARS-CoV-2infected Calu-3 cells, which showed responses associated with IFN I, II, or III signaling [13][14][15][16][17]; innate immunity, inflammation, and defense against virus [13,14]; TNF and IL-17 signaling [130], and signaling mediated by RIG-I/MDA5 [13,16]. In contrast, chemokine genes are generally up-regulated in infected Calu-3 cells [13][14][15]17,130], which were not found in our study (Supplementary File S1).…”

“…Our results are in line with other transcriptome studies conducted in SARS-CoV-2infected Calu-3 cells, which showed responses associated with IFN I, II, or III signaling [13][14][15][16][17]; innate immunity, inflammation, and defense against virus [13,14]; TNF and IL-17 signaling [130], and signaling mediated by RIG-I/MDA5 [13,16]. In contrast, chemokine genes are generally up-regulated in infected Calu-3 cells [13][14][15]17,130], which were not found in our study (Supplementary File S1). This transcriptional picture with the predominance of INF and chemokine genes and the enrichment of pathways associated with interferon response and innate immunity was also described for Calu-3 cells infected with other respiratory viruses, such as Rhinovirus (RV), Influenza A (IAV), and Influenza B (IBV) [137].…”

“…In addition, the TNF signaling KEGG pathway (hsa04668) was also significantly enriched in our infected samples, which is in line with previous studies [130]. This pathway included mainly up-regulated genes involved in TNF-p38 (CEBPB, TRAF2, RPSGKA4, and CREB5), TNF-JNK (FOS, JUN, and TRAF2), TNF-NF-κB (TRAF2, and NFKBIA), and TNF-IRF1 signaling pathways, which lead to the release of pro-inflammatory cytokines and apoptosis [131,132].…”

“…Thus, our results suggest the activation of the IL-17 signaling pathway by the ORF8 protein. The enrichment of the KEGG IL-17 signaling pathway in SARS-CoV-2-infected Calu-3 was also described in a transriptomic study by Sun et al [130].…”