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Comparison of Intracellular Transcriptional Response of NHBE Cells to Infection with SARS-CoV-2 Washington and New York Strains.
Scott, Tiana M; Solis-Leal, Antonio; Lopez, J Brandon; Robison, Richard A; Berges, Bradford K; Pickett, Brett E.
  • Scott TM; Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States.
  • Solis-Leal A; Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States.
  • Lopez JB; Population Health and Host-pathogen Interactions Programs, Texas Biomedical Research Institute, San Antonio, TX, United States.
  • Robison RA; Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States.
  • Berges BK; Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States.
  • Pickett BE; Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States.
Front Cell Infect Microbiol ; 12: 1009328, 2022.
Article in English | MEDLINE | ID: covidwho-2198710
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019 and caused a global pandemic resulting in millions of deaths and tens of millions of patients positive tests. While studies have shown a D614G mutation in the viral spike protein are more transmissible, the effects of this and other mutations on the host response, especially at the cellular level, are yet to be fully elucidated. In this experiment we infected normal human bronchial epithelial (NHBE) cells with the Washington (D614) strain or the New York (G614) strains of SARS-CoV-2. We generated RNA sequencing data at 6, 12, and 24 hours post-infection (hpi) 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 (DEGs), enriched Gene Ontology (GO) terms and dysregulated signaling pathways. We detected over 2,000 DEGs, over 600 GO terms, and 29 affected pathways between the two infections. Many of these entities play a role in immune signaling and response. A comparison between strains and time points showed a higher similarity between matched time points than across different time points with the same strain in DEGs and affected pathways, but found more similarity between strains across different time points when looking at GO terms. A comparison of the affected pathways showed that the 24hpi samples of the New York strain were more similar to the 12hpi samples of the Washington strain, with a large number of pathways related to translation being inhibited in both strains. These results suggest that the various mutations contained in the genome of these two viral isolates may cause distinct effects on the host transcriptional response in infected host cells, especially relating to how quickly translation is dysregulated after infection. This comparison of the intracellular host response to infection with these two SARS-CoV-2 isolates suggest that some of the mechanisms associated with more severe disease from these viruses could include virus replication, metal ion usage, host translation shutoff, host transcript stability, and immune inhibition.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Country/Region as subject: North America Language: English Journal: Front Cell Infect Microbiol Year: 2022 Document Type: Article Affiliation country: Fcimb.2022.1009328

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Country/Region as subject: North America Language: English Journal: Front Cell Infect Microbiol Year: 2022 Document Type: Article Affiliation country: Fcimb.2022.1009328