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| Status |
Public on Dec 22, 2008 |
| Title |
Analysis of wild-type and C mutant human HPIV1 and interferon beta treatment in human respiratory epithelial A549 cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
HPIV1 is an important respiratory pathogen in children and the most common cause of viral croup. We performed a microarray-based analysis of gene expression kinetics to examine how wild-type (wt) HPIV1 infection altered gene expression in human respiratory epithelial cells and what role IFN-beta played in this response. We similarly evaluated HPIV1-P(C-), a highly attenuated and apoptosis-inducing virus that does not express any of the four C proteins, and HPIV1-C(F170S), a less attenuated mutant that contains a single point mutation in C and, like wt HPIV1, does not efficiently induce apoptosis, to examine the role of the C proteins in controlling host gene expression. We also used this data to investigate whether the phenotypic differences between the two C mutants could be explained at the transcriptional level. Mutation or deletion of the C proteins of HPIV1 permitted the activation of over 2000 cellular genes that otherwise would be repressed by HPIV1 infection. Thus, the C proteins profoundly suppress the response of human respiratory cells to HPIV1 infection. Cellular pathways targeted by the HPIV1 C proteins were identified and their transcriptional control was analyzed using bioinformatics. Transcription factor binding sites for IRF and NF-kappaB were over-represented in some of the C protein targeted pathways, but other pathways were dominated by less known factors such as forkhead transcription factor FOXD1. Surprisingly, the host response to the C knockout and C(F170S) mutants was very similar, and thus the phenotypic differences between these two viruses could not be explained at the host cell transcriptional level.
Keywords: Time course; response to viral infection; response to IFN-beta
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| Overall design |
A549 cells were infected with wt HPIV1, C(F170S), or P(C-) in triplicate, and RNA was isolated at 6, 12, 24, and 48 hours. A549 cells were also treated with IFN-beta in triplicate, and RNA was isolated at 6 and 24 hours. Mock infection/treatment was performed in triplicate at each corresponding time point. Overall, 42 samples and microarrays were analyzed.
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| Contributor(s) |
Boonyaratanakornkit JB |
| Citation(s) |
19052086 |
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| Submission date |
Sep 04, 2008 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Jim Boonyaratanakornkit |
| E-mail(s) |
jim.boonyaratanakornkit@gmail.com
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| Phone |
301-594-2589
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| Organization name |
NIH - NIAID
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| Department |
LID
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| Lab |
RVS
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| Street address |
50 South Dr, Bldg 50, Rm 6513
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (42)
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| Relations |
| BioProject |
PRJNA112731 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12664_RAW.tar |
640.4 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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