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

Autor:	Bhargava A; Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus sensing and signaling Unit, 75015 Paris, France., Szachnowski U; CNRS UMR3244, Sorbonne University, PSL University, Institut Curie, Centre de Recherche, 75005 Paris, France., Chazal M; Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus sensing and signaling Unit, 75015 Paris, France., Foretek D; 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., Caval V; Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus sensing and signaling Unit, 75015 Paris, France., Aicher SM; Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus sensing and signaling Unit, 75015 Paris, France., Pipoli da Fonseca J; Institut Pasteur, Université de Paris, Biomics Platform, C2RT, 75015 Paris, France., Jeannin P; Institut Pasteur, Université de Paris, CNRS UMR 3569, Unité Épidémiologie et Physiopathologie des Virus Oncogènes, 75015 Paris, France., Beauclair G; Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91190 Gif-sur-Yvette, France., Monot M; Institut Pasteur, Université de Paris, Biomics Platform, C2RT, 75015 Paris, France., Morillon A; CNRS UMR3244, Sorbonne University, PSL University, Institut Curie, Centre de Recherche, 75005 Paris, France., Jouvenet N; Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus sensing and signaling Unit, 75015 Paris, France.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Nov 13; Vol. 26 (12), pp. 108449. Date of Electronic Publication: 2023 Nov 13 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.108449
Abstrakt:	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. Competing Interests: The authors declare that they have no competing interests. (© 2023 The Authors.)
Databáze:	MEDLINE
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