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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The 1918 PB2 protein, not HA, enhances the virulence of an avian influenza virus closely related to the 1918 pandemic virus through the inhibition of wnt signaling.

ABSTRACT: The purpose of this experiment was to understand the pathogenic role of individual 1918 genes on the host response to the 1918 pandemic influenza virus. We examined reassortant avian viruses nearly identical to the pandemic 1918 virus (1918-like avian virus) carrying either the 1918 HA or PB2 gene. Both genes enhanced 1918-like avian virus replication, but only the mammalian host adaptation of the 1918-like avian virus through reassortment of the 1918 PB2 led to increased lethality in mice. We demonstrate that 1918 PB2 enhances immune and inflammatory responses concomitant with increased cellular infiltration in the lung. We also show that 1918 PB2 expression results in the repression of both canonical and non-canonical Wnt signaling pathways which are crucial for inflammation mediated lung regeneration and repair. Five- to six-week-old female BALB/c mice (Jackson Laboratory) were used for the experiments. Isoflurane-anesthetized mice were intranasally inoculated with tenfold serial dilutions (three mice per dilution) of 1918, 1918-like avian, 1918 PB2/avian and 1918 HA/avian viruses. The dose required to kill 50% of mice (MLD50) was calculated using the Reed-Muench method. For analysis of virus growth and microarray profiling mice were intranasally inoculated with 10^4 PFU of virus (n=4/virus/timepoint) or PBS (n=3/timepoint). At days 1, 2 and 4 after infection, lungs were harvested from the infected mice. Lungs were processed for RNA extraction for microarray studies and virus titer determination.

ORGANISM(S): Mus musculus

SUBMITTER: Michael Katze

PROVIDER: E-GEOD-70502 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The purpose of this experiment was to understand the pathogenic role of individual 1918 genes on the host response to the 1918 pandemic influenza virus. We examined reassortant avian viruses nearly identical to the pandemic 1918 virus (1918-like avian virus) carrying either the 1918 HA or PB2 gene. Both genes enhanced 1918-like avian virus replication, but only the mammalian host adaptation of the 1918-like avian virus through reassortment of the 1918 PB2 led to increased lethality in mice. We demonstrate that 1918 PB2 enhances immune and inflammatory responses concomitant with increased cellular infiltration in the lung. We also show that 1918 PB2 expression results in the repression of both canonical and non-canonical Wnt signaling pathways which are crucial for inflammation mediated lung regeneration and repair.

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