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Publications

Journal Article Epublish 2 citations

PubMed: 38213785 DOI: 10.1016/j.isci.2023.108449

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

iScience 26(12):108449

Authors: Anvita Bhargava, Ugo Szachnowski, Maxime Chazal, Dominika Foretek, Vincent Caval, Sophie-Marie Aicher, Juliana Pipoli da Fonseca, Patricia Jeannin, Guillaume Beauclair, Marc Monot, Antonin Morillon, Nolwenn Jouvenet

Affiliations

  • Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus sensing and signaling Unit, 75015 Paris, France.
  • CNRS UMR3244, Sorbonne University, PSL University, Institut Curie, Centre de Recherche, 75005 Paris, France.
  • Institut Pasteur, Université de Paris, Biomics Platform, C2RT, 75015 Paris, France.
  • Institut Pasteur, Université de Paris, CNRS UMR 3569, Unité Épidémiologie et Physiopathologie des Virus Oncogènes, 75015 Paris, France.
  • Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91190 Gif-sur-Yvette, France.

Abstract

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.

MeSH

Infections, Rna, Cells, Genes, Lung, Sars Virus, Sars-Cov-2

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