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. 2023 Nov 13;26(12):108449.
doi: 10.1016/j.isci.2023.108449. eCollection 2023 Dec 15. Transcriptomic analysis of sorted lung cells revealed a proviral activity of the NF-κB pathway toward SARS-CoV-2
Anvita Bhargava 1 , Ugo Szachnowski 2 , Maxime Chazal 1 , Dominika Foretek 1 2 , Vincent Caval 1 , Sophie-Marie Aicher 1 , Juliana Pipoli da Fonseca 3 , Patricia Jeannin 4 , Guillaume Beauclair 5 , Marc Monot 3 , Antonin Morillon 2 , Nolwenn Jouvenet 1
Affiliations
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.
Keywords: Cell; Transcriptomics; Virology.
. 2023 Nov 13;26(12):108449.
doi: 10.1016/j.isci.2023.108449. eCollection 2023 Dec 15. Transcriptomic analysis of sorted lung cells revealed a proviral activity of the NF-κB pathway toward SARS-CoV-2
Anvita Bhargava 1 , Ugo Szachnowski 2 , Maxime Chazal 1 , Dominika Foretek 1 2 , Vincent Caval 1 , Sophie-Marie Aicher 1 , Juliana Pipoli da Fonseca 3 , Patricia Jeannin 4 , Guillaume Beauclair 5 , Marc Monot 3 , Antonin Morillon 2 , Nolwenn Jouvenet 1
Affiliations
- PMID: 38213785
- PMCID: PMC10783605
- DOI: 10.1016/j.isci.2023.108449
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.
Keywords: Cell; Transcriptomics; Virology.