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Dataset Details (GSE65075)

Superfund Research Program

Title: Acute lung injury results from innate sensing of viruses by an ER stress pathway

Accession Number: GSE65075

Link to Dataset:

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Expression profiling by array

Organism(s): Mus musculus

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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