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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.
Genes (Basel). 2020 07 07; 11(7)G

Abstract

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.

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Authors+Show Affiliations

Vishnubalaji R
Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha 34110, Qatar.
Shaath H
Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha 34110, Qatar. College of Health & Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha 34110, Qatar.
Alajez NM
Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha 34110, Qatar. College of Health & Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha 34110, Qatar.

MeSH

BetacoronavirusBiomarkersBronchiCOVID-19Cell DeathCell LineCluster AnalysisCoronavirus InfectionsEpithelial CellsGene Regulatory NetworksHumansImmunity, InnateInterferon-Stimulated Gene Factor 3, gamma SubunitLungPandemicsPneumonia, ViralRNA, Long NoncodingSARS-CoV-2TranscriptomeViral Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32646047

Citation

Vishnubalaji, Radhakrishnan, et al. "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." Genes, vol. 11, no. 7, 2020.
Vishnubalaji R, Shaath H, Alajez NM. 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. Genes (Basel). 2020;11(7).
Vishnubalaji, R., Shaath, H., & Alajez, N. M. (2020). 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. Genes, 11(7). https://doi.org/10.3390/genes11070760
Vishnubalaji R, Shaath H, Alajez NM. 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. Genes (Basel). 2020 07 7;11(7) PubMed PMID: 32646047.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Vishnubalaji,Radhakrishnan, AU - Shaath,Hibah, AU - Alajez,Nehad M, Y1 - 2020/07/07/ PY - 2020/06/12/received PY - 2020/06/28/revised PY - 2020/07/03/accepted PY - 2020/7/11/entrez PY - 2020/7/11/pubmed PY - 2020/7/17/medline KW - COVID-19 KW - IFN response KW - MAPK KW - SARS-CoV-2 KW - bronchial epithelial KW - gene expressions KW - immune response KW - lncRNAs KW - pathway analysis JF - Genes JO - Genes (Basel) VL - 11 IS - 7 N2 - 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. SN - 2073-4425 UR - https://www.unboundmedicine.com/medline/citation/32646047/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_ DB - PRIME DP - Unbound Medicine ER -