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| Status |
Public on Jul 06, 2015 |
| Title |
Acute lung injury results from innate sensing of viruses by an ER stress pathway |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Incursions of new pathogenic viruses into humans from animal reservoirs are occurring with alarming frequency. The molecular underpinnings of immune recognition, host responses, and pathogenesis in this setting arepoorly understood. We studied pandemic influenza viruses to determine the mechanism by which increasing glycosylation during evolution of surface proteins facilitates diminished pathogenicity in adapted viruses. ER stressduring infection with poorly glycosylated pandemic strains activated the unfolded protein response, leading to inflammation, acute lung injury, and mortality. Seasonal strains or viruses engineered to mimic adapted viruses displaying excess glycans on the hemagglutinin did not cause ER stress, allowing preservation of the lungs and survival. We propose that ER stress resultingfrom recognition of non-adapted viruses is utilized to discriminate “non-self” at the level of protein-processing and to activate immune responses, with unintended consequences on pathogenesis. Understanding this mechanism should improve strategies for treating acute lung injury from zoonotic viral infections.
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| |
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| Overall design |
Lung transcription analysis of Influenza A virus infected mice.
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| Contributor(s) |
Hrincius ER, Ledmann S, Finkelstein D, Vogel P, Gansebom S, Samarasinghe AE, You D, Cormier SA, McCullers JA |
| Citation(s) |
26051937 |
| Submission date |
Jan 18, 2015 |
| Last update date |
Feb 21, 2018 |
| Contact name |
David Finkelstein |
| E-mail(s) |
david.finkelstein@stjude.org
|
| Phone |
9014953931
|
| Organization name |
St Jude Children's Research Hospital
|
| Department |
Computational Biology
|
| Street address |
332 N. Lauderdale St.
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
|
| Samples (20)
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| Relations |
| BioProject |
PRJNA272883 |
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