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Article Dans Une Revue iScience Année : 2023

Transcriptomic analysis of sorted lung cells revealed a proviral activity of the NF-κB pathway toward SARS-CoV-2

Marc Monot

Résumé

Investigations of cellular responses to viral infection are commonly performed on mixed populations of infected and uninfected cells or using single-cell RNA sequencing, leading to inaccurate and low-resolution gene expression interpretations. Here, we performed deep polyA+ transcriptome analyses and novel RNA profiling of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected lung epithelial cells, sorted based on the expression of the viral spike (S) protein. Infection caused a massive reduction in mRNAs and long non-coding RNAs (lncRNAs), including transcripts coding for antiviral factors, such as interferons (IFNs). This absence of IFN signaling probably explained the poor transcriptomic response of bystander cells co-cultured with S+ ones. NF-κB pathway and the inflammatory response escaped the global shutoff in S+ cells. Functional investigations revealed the proviral function of the NF-κB pathway and the antiviral activity of CYLD, a negative regulator of the pathway. Thus, our transcriptomic analysis on sorted cells revealed additional genes that modulate SARS-CoV-2 replication in lung cells.
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Origine : Publication financée par une institution
Licence : CC BY NC ND - Paternité - Pas d'utilisation commerciale - Pas de modification

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pasteur-04455549 , version 1 (13-02-2024)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Anvita Bhargava, Ugo Szachnowski, Maxime Chazal, Dominika Foretek, Vincent Caval, et al.. Transcriptomic analysis of sorted lung cells revealed a proviral activity of the NF-κB pathway toward SARS-CoV-2. iScience, 2023, 26 (12), pp.108449. ⟨10.1016/j.isci.2023.108449⟩. ⟨pasteur-04455549⟩
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