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| Status |
Public on Sep 28, 2021 |
| Title |
The NF-κB transcriptional footprint is essential for SARS-CoV-2 replication |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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 factors 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.
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| Overall design |
(1) Independent biological triplicates of transformed lung alveolar (A549) cells transduced with a vector expressing human ACE2 infected with SARS-CoV-2 (USA-WA1/2020, MOI: 2) for 2/4/6/9/12/18/24 hours. Samples were examined by mRNA-seq. (2) Independent biological triplicates of transformed lung alveolar (A549) cells transduced with a vector expressing human ACE2 infected with SARS-CoV-2 (USA-WA1/2020, MOI: 0.01) for 24 hours. Samples were examined by scRNA-seq. (3) Independent biological triplicates of transformed lung alveolar (A549) cells transduced with a vector expressing human ACE2 infected with SARS-CoV-2 (USA-WA1/2020, MOI: 0.1) for 24 hours. Samples were examined by ATAC-seq.
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| Contributor(s) |
Nilsson-Payant BE, Uhl S, Grimont A, Doane AS, Cohen P, Patel RS, Higgins CA, Acklin JA, Bram Y, Chandar V, Blanco-Melo D, Panis M, Lim JK, Elemento O, Schwartz RE, Rosenberg BR, Chandwani R, tenOever BR |
| Citation(s) |
34523966 |
| Submission date |
Sep 21, 2021 |
| Last update date |
Oct 15, 2021 |
| Contact name |
Benjamin Erik Nilsson-Payant |
| E-mail(s) |
benjamin.nilsson-payant@twincore.de
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| Organization name |
TWINCORE Centre for Experimental and Clinical Infection Research
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| Department |
Experimental Virology
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| Street address |
Feodor-Lynen-Straße 7
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| City |
Hannover |
| ZIP/Postal code |
30625 |
| Country |
Germany |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL30173 |
NextSeq 2000 (Homo sapiens) |
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| Samples (48)
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| Relations |
| BioProject |
PRJNA764933 |
| SRA |
SRP338079 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE184536_ATACseq_Mock_1.bw |
442.1 Mb |
(ftp)(http) |
BW |
| GSE184536_ATACseq_Mock_2.bw |
402.2 Mb |
(ftp)(http) |
BW |
| GSE184536_ATACseq_SARSCoV2_1.bw |
441.9 Mb |
(ftp)(http) |
BW |
| GSE184536_ATACseq_SARSCoV2_2.bw |
543.6 Mb |
(ftp)(http) |
BW |
| GSE184536_ATACseq_SARSCoV2_3.bw |
550.7 Mb |
(ftp)(http) |
BW |
| GSE184536_mRNAseq_RawReadCounts.csv.gz |
981.9 Kb |
(ftp)(http) |
CSV |
| GSE184536_scRNAseq_barcodes.tsv.gz |
2.2 Mb |
(ftp)(http) |
TSV |
| GSE184536_scRNAseq_features.tsv.gz |
478.5 Kb |
(ftp)(http) |
TSV |
| GSE184536_scRNAseq_matrix.mtx.gz |
178.2 Mb |
(ftp)(http) |
MTX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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