Profiling transcription factor sub-networks in type I interferon signaling and in response to SARS-CoV-2 infection
Abstract Type I interferons (IFN α/β) play a central role in innate immunity to respiratory viruses, including coronaviruses. In this study, transcription factor profiling in the transcriptome was used to gain novel insights into the role of inducible transcription factors in response to type I interferon signaling in immune cells and in lung epithelial cells after SARS-CoV-2 infection. Modeling the interferon-inducible transcription factor mRNA data in terms of distinct sub-networks based on biological functions such as antiviral response, immune modulation, and cell growth revealed enrichment of specific transcription factors in mouse and human immune cells. Interrogation of multiple microarray datasets revealed that SARS-CoV-2 induced high levels of IFN-beta and interferon-inducible transcription factor mRNA in human lung epithelial cells. Transcription factor mRNA of the three sub-networks were differentially regulated in human lung epithelial cell lines after SARS-CoV-2 infection and in COVID-19 patients. A subset of type I interferon-inducible transcription factors and inflammatory mediators were specifically enriched in the lungs and neutrophils of Covid-19 patients. The emerging complex picture of type I IFN transcriptional regulation consists of a rapid transcriptional switch mediated by the Jak-Stat cascade and a graded output of the inducible transcription factor activation that enables temporal regulation of gene expression..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Computational and mathematical biophysics - 9(2021), 1 vom: 31. Dez., Seite 273-288 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ramana, Chilakamarti V. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Anmerkungen: |
© 2021 Chilakamarti V. Ramana et al., published by De Gruyter |
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| doi: |
10.1515/cmb-2020-0128 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Abstract Type I interferons (IFN α/β) play a central role in innate immunity to respiratory viruses, including coronaviruses. In this study, transcription factor profiling in the transcriptome was used to gain novel insights into the role of inducible transcription factors in response to type I interferon signaling in immune cells and in lung epithelial cells after SARS-CoV-2 infection. Modeling the interferon-inducible transcription factor mRNA data in terms of distinct sub-networks based on biological functions such as antiviral response, immune modulation, and cell growth revealed enrichment of specific transcription factors in mouse and human immune cells. Interrogation of multiple microarray datasets revealed that SARS-CoV-2 induced high levels of IFN-beta and interferon-inducible transcription factor mRNA in human lung epithelial cells. Transcription factor mRNA of the three sub-networks were differentially regulated in human lung epithelial cell lines after SARS-CoV-2 infection and in COVID-19 patients. A subset of type I interferon-inducible transcription factors and inflammatory mediators were specifically enriched in the lungs and neutrophils of Covid-19 patients. The emerging complex picture of type I IFN transcriptional regulation consists of a rapid transcriptional switch mediated by the Jak-Stat cascade and a graded output of the inducible transcription factor activation that enables temporal regulation of gene expression. | ||
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