Lack of effective treatment strategy and vaccine makes SARS-CoV-2 infection a big threat to mankind. Analyzing the host transcriptional changes in response to virus infection will help delineate the biological processes impacted by the virus and will potentially facilitate drug development. Using RNA seq datasets of virus infected lung cell lines A549 (infected with either SARS-CoV-2 or Influenza A virus (IAV)) and Calu3 (infected with either SARS-CoV-2 or MERS-CoV), we present a detailed analysis of genes expression changes in response to each of these viral infections. Upregulation of the antiviral interferon signaling was observed with all three viral infections. However, upregulation of the cytokine/inflammatory processes, downregulation of mitochondrial organization and respiration processes, and perturbation in the autophagic processes were specifically observed in SARS-CoV-2 infected cells, which were absent in IAV infected cells. Upregulation of the inflammatory processes was concordant with the gene expression signature of COVID-19 lungs and with inflammatory symptoms observed in severe cases of COVID-19 patients. Coexpression networks analysis also facilitated the identification of protein-protein interaction (PPI) subnetworks of genes in the inflammation and mitochondrial processes that were either coordinately up or downregulated in SARS-CoV-2 infected cells, respectively. Comparing the expression of marker genes of lung cell types from single cell RNA seq data with expression profile of A549 cells revealed that they likely represent the lung epithelial lineage cells. The cellular processes uniquely perturbed in infected cells that were identified in this analysis likely delineates lung epithelial cells response to the SARS-CoV-2 infection.
PathogenicityAs obligate parasites, the viruses, while evading the host cell immune response, should encode enough proteins to ensure replication, and spread, by relying on the host cell's machinery. These processes require an intricate series of interaction between the virus and host (9). While many of the elicited responses are common across pathogens, each virus also creates a unique transcriptional profile (10). Functional distinctions across viruses may arise due to distinct processes utilized by a virus for cellular entry, or for host immune system evasion, or for replication and dissemination (11). Severity of illness for SARS-CoV-2 infections is likely impacted by both the direct cytotoxic effects of the virus, and the effectiveness of the complex host response (12,13). While the immune response is essential to resolving the infection, dysregulation of the immune system can result in immunopathogenesis (14,15). A dysregulated immune response is caused by rapid viral replication, cytokine storms delayed interferon response, and macrophage infiltration and excessive proinflammatory cytokines (14). This immunopathogenesis mechanism is supported by the observation of decreased viral loads occurring with increased disease severity (6). However, efforts to unders...