Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Molecular signatures associated with Mx1-mediated resistance to highly pathogenic influenza virus infection: mechanisms of survival

ABSTRACT: Understanding the role of host factors during lethal influenza virus infection is critical to deciphering the events that will determine the fate of the host. One such factor is encoded by the Mx1 gene, which confers resistance to influenza virus infection. Here, we compared pathology and global gene expression profiles in lung tissue from BALB/c (Mx1(-)) and BALB•A2G-Mx1 mice (Mx1(+/+)) infected with the fully reconstructed 1918 pandemic influenza virus with an without interferon-alpha pretreatment. Mx1(+/+) mice showed less tissue damage than Mx(-) animals, and pathology and mortality were further reduced by treating the mice with interferon prior to infection. The goal of the global transcriptional profiling was to identify distinct molecular signatures associated with partial protection, complete protection, and the contribution of interferon to the host response. BALB/c mice carrying a defective allele of the Mx1 resistance gene or congenic Balb.A2G-Mx1 mice carrying the functional Mx1 allele. Half of the animals in each group were intranasally treated with 10,000 units of recombinant human IFN-α A/D (R&D Systems, Minneapolis, MN). Animals were anesthetized by IP injection and inoculated intranasally with 3.2 × 10^5 PFU (One hundred times 50% lethal dose (LD50)) of the reconstructed 1918 infectious virus diluted in 50 μl phosphate-buffered saline (PBS) or mock infected with PBS. To assess gene expression in response to r1918 virus with and without IFN treatment, lungs were harvested at 12hr, 24hr, and 72hr post-innoculation (n=3 per group at each time point). To assess gene expression in the context of IFN treatment only, lungs were harvested at 8h and 24hr post-treatment (n=3 per group at each time point). To assess gene expression without IFN or virus infection, lungs were harvested from mock-infected animals at 12h, 24h and 72hr from both Balb/c (n=2 per at each time point) and Mx1+/+ (n=3 at each time point).

ORGANISM(S): Mus musculus

SUBMITTER: Richard Green

PROVIDER: E-GEOD-35933 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Molecular signatures associated with Mx1-mediated resistance to highly pathogenic influenza virus infection: mechanisms of survival

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