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| Status |
Public on Nov 19, 2019 |
| Title |
Dexamethasone inhibits respiratory syncytial virus-driven mucus production while increasing viral replication without altering antiviral interferon signaling |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Purpose: To understand how dexamethasone has beneficial effects on reducing mucus production but inhibits viral defense mechanisms
Methods: RSV-infected mouse lungs and various cell lines, plus and minus dexamethason, were examined by RNAseq, and pathway analysis of differentially-expressed genes were compared
Results: Using RNA-seq we identified a subset of cytokines that were induced by RSV and repressed by dexamethasone. Interestingly, while RSV induced interferons (IFNs) and IFN stimulated genes (ISGs), dexamethasone treatment did not affect the expression of these genes or antiviral IFN signaling pathways as has been observed with glucocorticoid treatment of other respiratory viruses [13]. Using an unbiased approach, we found that certain RSV-driven gene expression networks and genes were specifically modulated by dexamethasone treatment. Importantly, dexamethasone also reduced RSV clearance in vivo, which correlated with a reduction in specific immune response markers.
Conclusion: Our results support the possibility that the beneficial anti-inflammatory effects of dexamethasone treatment are counterbalanced by the increased viral load in patients, accounting for the lack of clinical benefit derived from treatment during RSV infection.
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| Overall design |
Lungs from RSV-infected and dexamethasone treated or non-treated mice, or various cell lines infected and/or dexamethasone-treated were compared
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| Contributor(s) |
McAllister CS, Ansaldi D, Growcott EJ, Zhong Y, Quackenbush D, Wolff KC, Tanaseichuk O, Lelais G, Barnes SW, Federe GC, Luna F, Walker JR, Zhou Y, Kuhen KL |
| Citation(s) |
31929001 |
| Submission date |
Nov 12, 2019 |
| Last update date |
Feb 18, 2020 |
| Contact name |
John R Walker |
| E-mail(s) |
jwalker@gnf.org
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| Phone |
858-812-1636
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| Organization name |
Genomics Institute of the Novartis Research Foundation
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| Lab |
Genetics Core
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| Street address |
10675 John Jay Hopkins
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| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92121 |
| Country |
USA |
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| Platforms (2) |
| GPL15103 |
Illumina HiSeq 1000 (Mus musculus) |
| GPL15433 |
Illumina HiSeq 1000 (Homo sapiens) |
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| Samples (29)
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| Relations |
| BioProject |
PRJNA588982 |
| SRA |
SRP229586 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE140226_A549_H292_HBEC_201.txt.gz |
2.2 Mb |
(ftp)(http) |
TXT |
| GSE140226_NCI_H292_149.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| GSE140226_mouseLung_238.txt.gz |
3.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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