Genomic analysis of increased
host immune and cell death responses induced
by 1918 influenza virus
Kash JC, Tumpey TM, Proll SC, Carter V, Perwitasari O, Thomas MJ, Basler CF, Palese P, Taubenberger JK, García-Sastre A, Swayne DE, Katze MG. Nature. 2006 Oct 5;443(7111):578-81
A research team led by John Kash and Michael
Katze of the University of Washington School
of Medicine’s Department of Microbiology
has combined global gene expression analysis
with Ingenuity Pathway Analysis (IPA) to understand
the molecular basis of the extreme host response
induced by the 1918 influenza virus.
The team used gene expression analysis in
order to get a global view of the host response
in infected mice, and analyzed the data in
IPA to understand the functional consequences
of those gene expression changes. Utilizing
IPA’s Canonical Pathway and Network
features, the team was able to conclude that
infection with the 1918 influenza virus resulted
in significant activation of pro-inflammatory
and cell death responses, and that activation
of these pathways may be major contributors
to the severe immunopathology seen in mice
infected with the 1918 virus. A comparison
analysis run in IPA went on to reveal that
the biological responses most significantly
induced by infection with non-lethal strains
of the virus included cell-cycle and glutathione
metabolism pathways, both of which may contribute
to the less severe immunopathology seen in
mice infected those strains.
The combined genomics and IPA approach in this study contributes
to our understanding of the molecular basis
of host response to virulent influenza, and
may eventually lead to identification of novel
antiviral therapies.
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