Abstract
Different respiratory viruses induce virus-specific gene expression in the host. Recent evidence, including those presented here, suggests that genetically related isolates of influenza virus induce strain-specific host gene regulation in several animal models. Here, we identified systemic strain-specific gene expression signatures in ferrets infected with pandemic influenza A/California/07/2009, A/Mexico/4482/2009 or seasonal influenza A/Brisbane/59/2007. Using uncorrelated shrunken centroid classification, we were able to accurately identify the infecting influenza strain with a combined gene expression profile of 10 selected genes, independent of the severity of disease. Another gene signature, consisting of 7 genes, could classify samples based on lung pathology. Furthermore, we identified a gene expression profile consisting of 31 probes that could classify samples based on both strain and severity of disease. Thus, we show that expression-based analysis of non-infected tissue enables distinction between genetically related influenza viruses as well as lung pathology. These results open for development of alternative tools for influenza diagnostics.
Highlights
The disease caused by the pandemic H1N1 influenza strains (H1N1pdm) that emerged in 2009 differed from previously circulating seasonal strains
Diagnostic procedures based on gene expression profiling of non-infected blood cells have previously been used to discriminate between infections with different respiratory viruses as well as between symptomatic and asymptomatic subjects infected with influenza (H3N2) [5,6]
We hypothesized that strain-specific host gene response after infection with different, albeit genetically similar, influenza viruses would be sufficient to correctly identify the infectious strain using sophisticated statistical classification algorithms
Summary
The disease caused by the pandemic H1N1 influenza strains (H1N1pdm) that emerged in 2009 differed from previously circulating seasonal strains. Current diagnostic approaches used in most hospitals do not routinely discern between influenza strains with minor genetic differences. To establish the exact infectious strain, current procedures require sampling of virus during shedding and either sequencing or analysis using a set of strain-specific PCR primers, targeting the minute differences between strains. Diagnostic procedures based on gene expression profiling of non-infected blood cells have previously been used to discriminate between infections with different respiratory viruses as well as between symptomatic and asymptomatic subjects infected with influenza (H3N2) [5,6]. We hypothesized that strain-specific host gene response after infection with different, albeit genetically similar, influenza viruses would be sufficient to correctly identify the infectious strain using sophisticated statistical classification algorithms
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