Transcriptomic analysis of sorted lung cells revealed a proviral activity of the NF-κB pathway toward SARS-CoV-2
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
Anvita Bhargava
Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus sensing and signaling Unit, 75015 Paris, France
Ugo Szachnowski
CNRS UMR3244, Sorbonne University, PSL University, Institut Curie, Centre de Recherche, 75005 Paris, France
Maxime Chazal
Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus sensing and signaling Unit, 75015 Paris, France
Dominika Foretek
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
Vincent Caval
Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus sensing and signaling Unit, 75015 Paris, France
Sophie-Marie Aicher
Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus sensing and signaling Unit, 75015 Paris, France
Juliana Pipoli da Fonseca
Institut Pasteur, Université de Paris, Biomics Platform, C2RT, 75015 Paris, France
Patricia Jeannin
Institut Pasteur, Université de Paris, CNRS UMR 3569, Unité Épidémiologie et Physiopathologie des Virus Oncogènes, 75015 Paris, France
Guillaume Beauclair
Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91190 Gif-sur-Yvette, France
Marc Monot
Institut Pasteur, Université de Paris, Biomics Platform, C2RT, 75015 Paris, France
Antonin Morillon
CNRS UMR3244, Sorbonne University, PSL University, Institut Curie, Centre de Recherche, 75005 Paris, France; Corresponding author
Nolwenn Jouvenet
Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus sensing and signaling Unit, 75015 Paris, France; Corresponding author
Summary: 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.
