Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response

<p dir="ltr">The global spread of COVID-19, caused by pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for an imminent response from medical research communities to better understand this rapidly spreading infection. Employing multiple bioi...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Radhakrishnan Vishnubalaji (3563306) (author)
مؤلفون آخرون: Hibah Shaath (5599658) (author), Nehad M. Alajez (7397276) (author)
منشور في: 2020
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author Radhakrishnan Vishnubalaji (3563306)
author2 Hibah Shaath (5599658)
Nehad M. Alajez (7397276)
author2_role author
author
author_facet Radhakrishnan Vishnubalaji (3563306)
Hibah Shaath (5599658)
Nehad M. Alajez (7397276)
author_role author
dc.creator.none.fl_str_mv Radhakrishnan Vishnubalaji (3563306)
Hibah Shaath (5599658)
Nehad M. Alajez (7397276)
dc.date.none.fl_str_mv 2020-07-01T00:00:00Z
dc.identifier.none.fl_str_mv 10.3390/genes11070760
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Protein_Coding_and_Long_Noncoding_RNA_lncRNA_Transcriptional_Landscape_in_SARS-CoV-2_Infected_Bronchial_Epithelial_Cells_Highlight_a_Role_for_Interferon_and_Inflammatory_Response/25904206
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
Biomedical and clinical sciences
Cardiovascular medicine and haematology
Clinical sciences
Oncology and carcinogenesis
Bronchial epithelial
COVID-19
Gene expressions
IFN response
Immune response
LncRNAs
MAPK
Pathway analysis
SARS-CoV-2
dc.title.none.fl_str_mv Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">The global spread of COVID-19, caused by pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for an imminent response from medical research communities to better understand this rapidly spreading infection. Employing multiple bioinformatics and computational pipelines on transcriptome data from primary normal human bronchial epithelial cells (NHBE) during SARS-CoV-2 infection revealed activation of several mechanistic networks, including those involved in immunoglobulin G (IgG) and interferon lambda (IFNL) in host cells. Induction of acute inflammatory response and activation of tumor necrosis factor (TNF) was prominent in SARS-CoV-2 infected NHBE cells. Additionally, disease and functional analysis employing ingenuity pathway analysis (IPA) revealed activation of functional categories related to cell death, while those associated with viral infection and replication were suppressed. Several interferon (IFN) responsive gene targets (IRF9, IFIT1, IFIT2, IFIT3, IFITM1, MX1, OAS2, OAS3, IFI44 and IFI44L) were highly upregulated in SARS-CoV-2 infected NBHE cell, implying activation of antiviral IFN innate response. Gene ontology and functional annotation of differently expressed genes in patient lung tissues with COVID-19 revealed activation of antiviral response as the hallmark. Mechanistic network analysis in IPA identified 14 common activated, and 9 common suppressed networks in patient tissue, as well as in the NHBE cell model, suggesting a plausible role for these upstream regulator networks in the pathogenesis of COVID-19. Our data revealed expression of several viral proteins in vitro and in patient-derived tissue, while several host-derived long noncoding RNAs (lncRNAs) were identified. Our data highlights activation of IFN response as the main hallmark associated with SARS-CoV-2 infection in vitro and in human, and identified several differentially expressed lncRNAs during the course of infection, which could serve as disease biomarkers, while their precise role in the host response to SARS-CoV-2 remains to be investigated.</p><h2>Other Information</h2><p dir="ltr">Published in: Genes<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/genes11070760" target="_blank">https://dx.doi.org/10.3390/genes11070760</a></p>
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identifier_str_mv 10.3390/genes11070760
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spelling Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory ResponseRadhakrishnan Vishnubalaji (3563306)Hibah Shaath (5599658)Nehad M. Alajez (7397276)Biological sciencesGeneticsBiomedical and clinical sciencesCardiovascular medicine and haematologyClinical sciencesOncology and carcinogenesisBronchial epithelialCOVID-19Gene expressionsIFN responseImmune responseLncRNAsMAPKPathway analysisSARS-CoV-2<p dir="ltr">The global spread of COVID-19, caused by pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for an imminent response from medical research communities to better understand this rapidly spreading infection. Employing multiple bioinformatics and computational pipelines on transcriptome data from primary normal human bronchial epithelial cells (NHBE) during SARS-CoV-2 infection revealed activation of several mechanistic networks, including those involved in immunoglobulin G (IgG) and interferon lambda (IFNL) in host cells. Induction of acute inflammatory response and activation of tumor necrosis factor (TNF) was prominent in SARS-CoV-2 infected NHBE cells. Additionally, disease and functional analysis employing ingenuity pathway analysis (IPA) revealed activation of functional categories related to cell death, while those associated with viral infection and replication were suppressed. Several interferon (IFN) responsive gene targets (IRF9, IFIT1, IFIT2, IFIT3, IFITM1, MX1, OAS2, OAS3, IFI44 and IFI44L) were highly upregulated in SARS-CoV-2 infected NBHE cell, implying activation of antiviral IFN innate response. Gene ontology and functional annotation of differently expressed genes in patient lung tissues with COVID-19 revealed activation of antiviral response as the hallmark. Mechanistic network analysis in IPA identified 14 common activated, and 9 common suppressed networks in patient tissue, as well as in the NHBE cell model, suggesting a plausible role for these upstream regulator networks in the pathogenesis of COVID-19. Our data revealed expression of several viral proteins in vitro and in patient-derived tissue, while several host-derived long noncoding RNAs (lncRNAs) were identified. Our data highlights activation of IFN response as the main hallmark associated with SARS-CoV-2 infection in vitro and in human, and identified several differentially expressed lncRNAs during the course of infection, which could serve as disease biomarkers, while their precise role in the host response to SARS-CoV-2 remains to be investigated.</p><h2>Other Information</h2><p dir="ltr">Published in: Genes<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/genes11070760" target="_blank">https://dx.doi.org/10.3390/genes11070760</a></p>2020-07-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/genes11070760https://figshare.com/articles/journal_contribution/Protein_Coding_and_Long_Noncoding_RNA_lncRNA_Transcriptional_Landscape_in_SARS-CoV-2_Infected_Bronchial_Epithelial_Cells_Highlight_a_Role_for_Interferon_and_Inflammatory_Response/25904206CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259042062020-07-01T00:00:00Z
spellingShingle Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response
Radhakrishnan Vishnubalaji (3563306)
Biological sciences
Genetics
Biomedical and clinical sciences
Cardiovascular medicine and haematology
Clinical sciences
Oncology and carcinogenesis
Bronchial epithelial
COVID-19
Gene expressions
IFN response
Immune response
LncRNAs
MAPK
Pathway analysis
SARS-CoV-2
status_str publishedVersion
title Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response
title_full Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response
title_fullStr Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response
title_full_unstemmed Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response
title_short Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response
title_sort Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response
topic Biological sciences
Genetics
Biomedical and clinical sciences
Cardiovascular medicine and haematology
Clinical sciences
Oncology and carcinogenesis
Bronchial epithelial
COVID-19
Gene expressions
IFN response
Immune response
LncRNAs
MAPK
Pathway analysis
SARS-CoV-2