Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes including CSF2, IL32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host-pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19. Ferrarini & Lal et al. developed a novel bioinformatic pipeline to explore how SARS-CoV-2 interacts with human respiratory cells using public available host gene expression and viral genome sequence data. Several human genes and proteins were predicted to play a role in the viral life cycle and the host response to SARS-CoV-2 infection.

Automated summary

Researchers analyzed public data to understand how SARS-CoV-2 interacts with human respiratory cells, identifying specific gene and element changes in infected cells. Predicted interactions between viral and human RNA-binding proteins were noted, along with a viral sequence variant linked to age.