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| Status |
Public on Nov 29, 2020 |
| Title |
Global transcriptome analysis of Autophagy and mTOR pathway activation by Influenza A virus in lung A549 cells |
| Organisms |
Homo sapiens; Influenza A virus (A/Port Chalmers/1/1973(H3N2)) |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Here we compare transcriptome dynamics in human lung carcinoma cells A549 infected with Influenza virus A/Port Chalmers/1/73 (H3N2) at two different virus to host cell ratios: multiplicity of infection (MOI) 1 and 5. Our goal was to outline the activation profiles of two main host pro-survival mechanisms, autophagy and mTORC2, co-opted by the virus to effectively complete the replication cycle, amplify, and release of infectious particles. We found that at high virus load MOI5 autophagy, a stress response mechanisms that postpones mammalian cell death, was activated and inhibited within 1 hour of infection. Autophagy downregulation was quickly followed by the activation of genes regulating mTORC2, a secondary cell survival mechanism promoting low capacity of cellular metabolism by inhibition of mTORC1, a main regulator of protein synthesis activating ribosomal elongation factors. At lower MOI (1) autophagy activation followed the virus replication cycle. We found that ULK1 gene expression was gradually upregulated upon Influenza virus A infection at MOI1 together with the activation of key regulators of mTORC1. Such results was not expected since mTORC1 inhibits autophagy activation pathway on post-transcription level through phosphorylation of ULK1.
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| Overall design |
Infection of A549 cells at two MOIs (1 and5) and sample collection at early (1,3, and 4h), mid (6, 8h), and late (12h) phases of Influenza replication cycle. NG RNAseq was applied on total RNA from virus infected cells. The transcriptomics results were validated by Western blot-based targeted proteomics analysis.
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| Contributor(s) |
Micheva-Viteva S, Bell T, Xi G, Starkenburg S |
| Citation(s) |
34931347 |
| |
| Submission date |
Nov 28, 2020 |
| Last update date |
Aug 02, 2022 |
| Contact name |
Sofiya N Micheva-Viteva |
| E-mail(s) |
sviteva@lanl.gov
|
| Phone |
505 606 1722
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| Organization name |
Los Alamos National Laboratory
|
| Department |
Bioscience
|
| Street address |
Los Alamos National Lab
|
| City |
Los Alamos |
| State/province |
New Mexico |
| ZIP/Postal code |
87545 |
| Country |
USA |
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| Platforms (2) |
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
| GPL29455 |
Illumina MiSeq (Homo sapiens; Influenza A virus (A/Port Chalmers/1/1973(H3N2))) |
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| Samples (27)
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| Relations |
| BioProject |
PRJNA681319 |
| SRA |
SRP294598 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE162295_PolyA_1h_PolyA_12h_CDS_et.csv.gz |
836.0 Kb |
(ftp)(http) |
CSV |
| GSE162295_PolyA_1h_PolyA_3h_CDS_et.csv.gz |
838.8 Kb |
(ftp)(http) |
CSV |
| GSE162295_PolyA_1h_PolyA_4h_CDS_et.csv.gz |
836.5 Kb |
(ftp)(http) |
CSV |
| GSE162295_PolyA_1h_PolyA_6h_CDS_et.csv.gz |
842.9 Kb |
(ftp)(http) |
CSV |
| GSE162295_PolyA_1h_PolyA_8h_CDS_et.csv.gz |
855.1 Kb |
(ftp)(http) |
CSV |
| GSE162295_mock_PolyA_12h_PolyA_12h_CDS_et.csv.gz |
859.1 Kb |
(ftp)(http) |
CSV |
| GSE162295_mock_PolyA_4h_PolyA_4h_CDS_et.csv.gz |
863.6 Kb |
(ftp)(http) |
CSV |
| GSE162295_mock_PolyA_8h_PolyA_8h_CDS_et.csv.gz |
860.8 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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