RNA-sequencing unravels unique host-response to infection with SARS-CoV-2
Respirology
; 28(Supplement 2):106, 2023.
Article
in English
| EMBASE | ID: covidwho-2314408
ABSTRACT
Introduction/Aim:
As the causative agent of COVID-19, SARS-CoV-2 remains a global cause for concern. Compared to other highly pathogenic coronaviruses (SARS-CoV and MERS-CoV), SARS-CoV-2 exhibits stronger transmissibility but less lethality, indicating that SARS-CoV-2 displays unique characteristics, despite the partial genomic proximity. Thus, we aim to employ RNA sequencing to define transcriptional differences in epithelial responses following infection with SARS-CoV-2 compared to pathogenic SARS-CoV and MERS-CoV, and low pathogenic HCoV-229E. Method(s) Primary human bronchial epithelial cells (PBEC) were differentiated for 6 weeks at the air-liquid interface (ALI) before parallel infection by the 4 different coronaviruses (n = 4). After infection following apical application of coronaviruses at low dose (MOI 0.1), cells were harvested for bulk RNA sequencing. Gene were considered significant with a fold change (FC) > 2 and false discovery rate of FDR < 0.05. Inhibitor experiments were conducted on CALU-3 cells using DIM-C-pPhOH 10 muM (NR4A1 antagonist), Sp600125 10 muM (JNK inhibitor), T-5224 10 muM (AP-1 transcription factor inhibitor) and Cytosporone B (CsB 5 muM;NR4A1 agonist) preincubated for 1 h with these compounds and subsequently infected with SARS-CoV-2 or MERS-CoV (MOI of 1). Samples were collect 24 h later for PCR. Result(s) PCR and RNA-Seq demonstrated that all tested coronaviruses efficiently infected ALI-PBEC and replicated over 72 h (p < 0.05). RNA sequencing analysis revealed that infection with SARS-CoV, MERS-CoV and HCoV-229E resulted in largely similar transcriptional responses by the epithelial cells. However, whereas infection with these viruses was accompanied by an increased expression of genes associated with JNK/AP-1 signalling, including FOS, FOSB and NR4A1 (FC > 1, FDR < 0.05), no such increase was observed following SARS-CoV-2 infection. Further, we found that an NR4A1 antagonist reduced viral replication of MERS and SARs-CoV-2 100-fold in Calu-3 cells. Conclusion(s) In conclusion, these data suggest that SARS-CoV-2-infected ALI-PBEC exhibit a unique transcriptional response compared to other coronaviruses, which might relate to the pathogenicity of the virus.
Calu-3 cell line; case report; clinical article; conference abstract; coronavirus disease 2019; false discovery rate; gene expression; genetic susceptibility; genetic transcription; HBEC cell line (bronchial epithelium); human; human cell; Human coronavirus 229E; immune response; low drug dose; Middle East respiratory syndrome coronavirus; multiplicity of infection; nonhuman; pathogenicity; polymerase chain reaction; protein expression; RNA sequencing; SARS coronavirus; Severe acute respiratory syndrome coronavirus 2; signal transduction; virus replication; anthra[1; 9 cd]pyrazol 6(2h) one; endogenous compound; nuclear receptor Nur77; stress activated protein kinase; transcription factor AP 1; transcription factor FosB
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Respirology
Year:
2023
Document Type:
Article
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