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The NF-κB Transcriptional Footprint Is Essential for SARS-CoV-2 Replication
- Source :
- Journal of Virology
- Publication Year :
- 2021
-
Abstract
- SARS-CoV-2, the etiological agent of COVID-19, is characterized by a delay in type I interferon (IFN-I)-mediated antiviral defenses alongside robust cytokine production. Here, we investigate the underlying molecular basis for this imbalance and implicate virus-mediated activation of NF-κB in the absence of other canonical IFN-I-related transcription factors. Epigenetic and single-cell transcriptomic analyses show a selective NF-κB signature that was most prominent in infected cells. Disruption of NF-κB signaling through the silencing of the NF-κB transcription factor p65 or p50 resulted in loss of virus replication that was rescued upon reconstitution. These findings could be further corroborated with the use of NF-κB inhibitors, which reduced SARS-CoV-2 replication in vitro. These data suggest that the robust cytokine production in response to SARS-CoV-2, despite a diminished IFN-I response, is the product of a dependency on NF-κB for viral replication. IMPORTANCE The COVID-19 pandemic has caused significant mortality and morbidity around the world. Although effective vaccines have been developed, large parts of the world remain unvaccinated while new SARS-CoV-2 variants keep emerging. Furthermore, despite extensive efforts and large-scale drug screenings, no fully effective antiviral treatment options have been discovered yet. Therefore, it is of the utmost importance to gain a better understanding of essential factors driving SARS-CoV-2 replication to be able to develop novel approaches to target SARS-CoV-2 biology.
- Subjects :
- Epigenomics
medicine.medical_treatment
Immunology
Biology
Virus Replication
Microbiology
NF-κB
Transcriptome
chemistry.chemical_compound
Interferon
Virology
Chlorocebus aethiops
medicine
Gene silencing
Animals
Humans
Epigenetics
Transcription factor
Vero Cells
Host Microbial Interactions
SARS-CoV-2
Transcription Factor RelA
COVID-19
Cell biology
Virus-Cell Interactions
Cytokine
HEK293 Cells
Viral replication
chemistry
Gene Expression Regulation
A549 Cells
Insect Science
Interferon Type I
Cytokines
Single-Cell Analysis
medicine.drug
HeLa Cells
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 10985514
- Volume :
- 95
- Issue :
- 23
- Database :
- OpenAIRE
- Journal :
- Journal of virology
- Accession number :
- edsair.doi.dedup.....b7a590a5030650165d61fc1a95ca0cc2