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,Hibah Shaath,Nehad M Alajez

doi:10.3390/genes11070760

Radhakrishnan Vishnubalaji, Hibah Shaath + Show 1 more

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https://doi.org/10.3390/genes11070760

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Journal: Genes	Publication Date: Jul 7, 2020
Citations: 106	License type: CC BY 4.0

Affiliation: Hamad bin Khalifa University, Qatar Foundation

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.

Highlights

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) was declared a global pandemic by the World Health Organization (WHO) onGenes 2020, 11, 760; doi:10.3390/genes11070760 www.mdpi.com/journal/genes11 March 2020 [1,2]
SARS-CoV-2 is the seventh coronavirus which has led to human disease, it is the third strain to surpass common cold like symptoms, all three deriving from the β-coronavirus genus [4], with the first and second resulting in endemics in recent history [5]
Severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) breakouts were reported in Southern China in 2003 and Saudi Arabia in 2012, respectively

Summary

Introduction

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) was declared a global pandemic by the World Health Organization (WHO) onGenes 2020, 11, 760; doi:10.3390/genes11070760 www.mdpi.com/journal/genes11 March 2020 [1,2]. Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus. SARS-CoV-2 is the seventh coronavirus which has led to human disease, it is the third strain to surpass common cold like symptoms, all three deriving from the β-coronavirus genus [4], with the first and second resulting in endemics in recent history [5]. Severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) breakouts were reported in Southern China in 2003 and Saudi Arabia in 2012, respectively. Genomic sequencing of SARS-CoV and MERS-CoV showed approximately 79% and 50% similarities with SARS-CoV-2, respectively [6]. Mathematical algorithms show that SARS-CoV-2 has a high estimated basic reproductive number (R0 ), reported as high as 6.49 (mean; 3.28), exceeding WHO estimations of 2.5 [8]

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