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Series GSE62169 Query DataSets for GSE62169
Status Public on Nov 03, 2014
Title NS1-mediated inhibition of c-Abl results in acute lung injury and priming for bacterial co-infections; insights into 1918 H1N1 pandemic
Organism Mus musculus
Experiment type Expression profiling by array
Summary NS1 proteins from avian influenza viruses like the 1918 pandemic NS1 are capable of inhibiting the key signaling integrator c-Abl (Abl1), resulting in massive cytopathic cell alterations. In the current study, we addressed the consequences of NS1-mediated alteration of c-Abl on acute lung injury and pathogenicity. Comparing isogenic strains that differ only in their ability to inhibit c-Abl, we observed elevated pathogenicity for the c-Abl-inhibiting virus. NS1-mediated block of c-Abl resulted in severe lung pathology and massive edema formation and facilitated secondary bacterial pneumonia. This phenotype was independent of differences in replication and immune responses, defining it as an NS1 virulence mechanism distinct from its canonical functions. Microarray analysis revealed extensive down-regulation of genes involved in cell integrity and vascular endothelial regulation. In conclusion, NS1 protein-mediated blockade of c-Abl signaling drives acute lung injury and primes for bacterial co-infections revealing potential insights into the pathogenicity of the 1918 pandemic virus.
 
Overall design Lung transcription analysis of Influenza A virus infected mice.
 
Contributor(s) Hrincius ER, Liedmann S, Finkelstein D, Vogel P, Gansebom S, Ehrhardt C, Ludwig S, Hains DS, Webby R, McCullers JA
Citation(s) 25367299
Submission date Oct 08, 2014
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
 
Platforms (1)
GPL16570 [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]
Samples (9)
GSM1520893 PBS_eh0016
GSM1520894 PBS_eh0017
GSM1520895 PBS_eh0018
Relations
BioProject PRJNA263363

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE62169_RAW.tar 89.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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