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| Status |
Public on May 26, 2017 |
| Title |
Rhinovirus infection results in stronger and more persistent genomic dysregulation: evidence for altered innate immune response in asthmatics at baseline, early in infection, and during convalescence |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Rhinovirus (HRV) is associated with the large majority of virus-induced asthma exacerbations in children and young adults, but the mechanisms remain poorly defined.
Methods: Asthmatics and non-asthmatic controls were inoculated with HRV-A16, and nasal epithelial samples were obtained 7 days before, 36 hours after, and 7 days after viral inoculation. RNA was extracted and subjected to RNA-seq analysis.
Results: At baseline, 57 genes were differentially expressed between asthmatics and controls, and the asthmatics had decreased expression of viral replication inhibitors and increased expression of genes involved in inflammation. At 36 hours (before the emergence of peak symptoms), 1329 genes were significantly altered from baseline in the asthmatics compared to 62 genes in the controls. At this time point, asthmatics lacked an increase in IL-10 signaling observed in the controls. At 7 days following HRV inoculation, 222 genes were significantly dysregulated in the asthmatics, whereas only 4 genes were dysregulated among controls. At this time point, the controls but not asthmatics demonstrated upregulation of SPINK5.
Conclusions: As judged by the magnitude and persistence of dysregulated genes, asthmatics have a substantially different host response to HRV-A16 infection compared with non-asthmatic controls. Gene expression differences illuminate biologically plausible mechanisms that contribute to a better understanding of the pathogenesis of HRV-induced asthma exacerbations.
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| Overall design |
Comparison of gene dysregulation in adult asthmatics and healthy controls at baseline and following human Rhinovirus inoculation.
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| Contributor(s) |
Khurana Hershey GK, Heymann PW, Nguyen HT, Steinke JW, Turner RB, Woodfolk JA, Platts-Mills TA, Martin L, He H, Biagini-Myers J, Lindsey M, Sivaprasad U, Medvedovic M, Mahi N, Carper H, Murphy DD, Patrie J |
| Citation(s) |
28552993 |
| Submission date |
Apr 11, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Gurjit Khurana Hershey |
| E-mail(s) |
gurjit.hershey@cchmc.org
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| Phone |
513-636-7054
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| Organization name |
Cincinnat Children's Hospital Medical Center
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| Department |
Division of Asthma Research
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| Street address |
3333 Burnet Avenue
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| City |
Cincinnati |
| State/province |
Ohio |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (1) |
| GPL15433 |
Illumina HiSeq 1000 (Homo sapiens) |
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| Samples (33)
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| Relations |
| BioProject |
PRJNA382595 |
| SRA |
SRP103819 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE97668_RawCount.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
| GSE97668_countsTable.txt.gz |
3.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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