SARS-CoV-2 variants induce increased inflammatory gene expression but reduced interferon responses and heme synthesis as compared with wild type strains.
ALAS2
Delta variant
EGR1
ISG
SARS-CoV-2
Variants of concern
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 10 2024
28 10 2024
Historique:
received:
21
07
2024
accepted:
14
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
SARS-CoV-2 variants of concern (VOC) have been associated with increased viral transmission and disease severity. We investigated the mechanisms of pathogenesis caused by variants using a host blood transcriptome profiling approach. We analysed transcriptional signatures of COVID-19 patients comparing those infected with wildtype (wt), alpha, delta or omicron strains seeking insights into infection in Asymptomatic cases.Comparison of transcriptional profiles of Symptomatic and Asymptomatic COVID-19 cases showed increased differentially regulated gene (DEGs) of inflammatory, apoptosis and blood coagulation pathways, with decreased T cell and Interferon stimulated genes (ISG) activation. Between SARS-CoV-2 strains, an increasing number of DEGs occurred in comparisons between wt and alpha (196), delta (1425) or, omicron (2313) infections. COVID-19 cases with alpha or, delta variants demonstrated suppression transcripts of innate immune pathways. EGR1 and CXCL8 were highly upregulated in those infected with VOC; heme biosynthetic pathway genes (ALAS2, HBB, HBG1, HBD9) and ISGs were downregulated. Delta and omicron infections upregulated ribosomal pathways, reflecting increased viral RNA translation. Asymptomatic COVID-19 cases infected with delta infections showed increased cytokines and ISGs expression. Overall, increased inflammation, with reduced host heme synthesis was associated with infections caused by VOC infections, with raised type I interferon in cases with less severe disease.
Identifiants
pubmed: 39468120
doi: 10.1038/s41598-024-76401-1
pii: 10.1038/s41598-024-76401-1
doi:
Substances chimiques
Heme
42VZT0U6YR
Interferons
9008-11-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25734Subventions
Organisme : Higher Education Commission, Pakistan
ID : GCF-913
Organisme : Higher Education Commission, Pakistan
ID : GCF-913
Organisme : Higher Education Commission, Pakistan
ID : GCF-913
Organisme : Higher Education Commission, Pakistan
ID : GCF-913
Informations de copyright
© 2024. The Author(s).
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