Regulation of early growth response-1 (Egr-1) gene expression by Stat1-independent type I interferon signaling and respiratory viruses

Autor: Ramana Chilakamarti V., Das Bikul
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Computational and Mathematical Biophysics, Vol 9, Iss 1, Pp 289-303 (2021)
Druh dokumentu: article
ISSN: 2544-7297
2020-0129
DOI: 10.1515/cmb-2020-0129
Popis: Respiratory virus infection is one of the leading causes of death in the world. Activation of the Jak-Stat pathway by Interferon-alpha/beta (IFN-α/β) in lung epithelial cells is critical for innate immunity to respiratory viruses. Transcriptional factor profiling in the transcriptome and RNA analysis revealed that Early growth response-1 (EGR1/Egr-1) was rapidly induced by IFN-α/β and Toll-like receptor (TLR) ligands in multiple cell types. Studies in mutant cell lines lacking components of the interferon-stimulated gene factor complex (ISGF-3) revealed that IFN-β induction of Egr-1 was independent of Stat1, Stat2, or Irf9. Activation of the Mek/Erk-1/2 pathway was implicated in the rapid induction of Egr-1 by IFN-β in serum-starved mouse lung epithelial cells. Interrogation of multiple microarray datasets revealed that respiratory viruses including coronaviruses induced IFN-β and regulated Egr-1 expression in human lung cell lines. Furthermore, bioinformatic analysis revealed that type I interferon-stimulated genes and Egr-1 inducible genes including transcription factors, mediators of cell growth, and chemokines were differentially regulated in the human lung cell lines after coronavirus infection, and in the lung biopsies of COVID-19 patients.
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