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Comparative transcriptomic analysis of acute host responses during 2009 pandemic H1N1 influenza infection in mouse, macaque, and swine (mouse dataset)

ABSTRACT: Background: The 2009 pandemic H1N1 influenza virus emerged in swine and quickly became a major global health threat. In mouse, non-human primate, and swine infection models, the pH1N1 virus efficiently replicates in the lung and induces pro-inflammatory host responses; however, whether similar or different cellular pathways were impacted by pH1N1 virus across independent infection models remains to be further defined. To address this, we have performed a comparative transcriptomic analysis of acute host responses to a single pH1N1 influenza virus, A/California/04/2009 (CA04), in the lung of mice, macaques and swine. Results: Despite similarities in the clinical course, we observed differences in inflammatory molecules elicited, and the kinetics of their gene expression changes across all three species. The retinoid X receptor (RXR) signaling pathway controlling pro-inflammatory and metabolic processes was differentially regulated during infection in each species, though the heterodimeric RXR partner, pathway associated signaling molecules, and gene expression patterns differed in each species. Conclusions: By comparing transcriptional changes in the context of clinical and virological measures, we identified differences in the host transcriptional response to pH1N1 virus across independent models of acute infection. Antiviral resistance and the emergence of new influenza viruses have placed more focus on developing drugs that target the immune system. Underlying overt clinical disease are molecular events that suggest therapeutic targets identified in one host may not be appropriate in another. The goal of this experiment was to use global gene expression profiling to understand mouse lung cellular responses to pandemic H1N1 influenza A/Californica/04/2009 virus infection. Six-to-eight-week-old female BALB/c mice were anesthetized and inoculated with either 50 μl of phosphate-buffered saline (PBS; Mock) or with 10^6 pfu of pandemic H1N1 influenza A/California/04/2009 virus in a 50 μl volume, and whole lungs were collected at days 1, 3 and 5 post-inoculation. Lung samples from 9 animals for the infection group were used for array analysis, three animals per time point. Lung samples from 8 animals for the mock group were used for array analysis, three animals for the day 1 and 3 time points and 2 animals for the day 5 time point.

ORGANISM(S): Mus musculus  

SUBMITTER: Michael G Katze   Terrence M Tumpey  Sarah E Belisle  Juergen A Richt  Richard Roy Green  Wenjun Ma  Heinz Feldmann  Jennifer Tisoncik Go  Nicolas Tchitchek 

PROVIDER: E-GEOD-40091 | ArrayExpress | 2012-08-13



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