Timecourse of SARS-CoV-2 Infection with New York & Washington Isolates

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that was first reported in Wuhan, China in December of 2019 and has since caused a global pandemic resulting in millions of deaths and tens of millions of patients testing positive for infection. Analysis of different viral strains has identified a D614G change in the spike protein that is correlated with the virus becoming more transmissible. While studies have shown G614 viruses to be more transmissible, the effects of this mutation on the host response, especially on the cellular level, are yet to be fully elucidated. In this experiment we infected NHBE cells with the Washington (D614) strain or the New York (G614) strains of SARS-CoV-2. We generated RNA sequencing data at three different time points to improve our understanding of how the intracellular host response differs between infections with these two strains. We analyzed these data with a bioinformatics pipeline that identifies differentially expressed genes, enriched Gene Ontology terms and dysregulated signaling pathways. We detected over 2,000 differentially expressed genes, over 600 Gene Ontology terms, and 29 affected pathways between the two treatments. Many of these entities play a role in immune signaling and response. When comparing the different strains and different time points we found more overall similarities between matched time points than across different time points with the same strain. When specifically comparing the affected pathways, we saw that the 24hr time point of the New York strain was more similar to the 12hr time point of the Washington strain with a large number of pathways related to translation being inhibited in both strains at these time points. These results suggest that D614G substitution in the spike protein, combined with other nonsynonymous changes in the viral gene products cause distinct responses in infected host cells, especially relating to how quickly translation is dysregulated after infection. These observed differences in the intracellular host response to infection could play a role in driving the increase in pathogenicity and mortality seen in the New York outbreaks versus the Washington outbreaks at the beginning of the SARS-CoV-2 pandemic.

ORGANISM(S): Homo sapiens

PROVIDER: GSE207923 | GEO | 2022/09/06

REPOSITORIES: GEO