The NF-κB Transcriptional Footprint Is Essential for SARS-CoV-2 Replication.
J Virol
; 95(23): e0125721, 2021 11 09.
Article
in English
| MEDLINE | ID: covidwho-1410202
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Replication
/
Interferon Type I
/
Cytokines
/
Transcription Factor RelA
/
Transcriptome
/
SARS-CoV-2
/
COVID-19
Type of study:
Etiology study
Topics:
Vaccines
/
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
J Virol
Year:
2021
Document Type:
Article
Affiliation country:
JVI.01257-21
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