Searching for a Lifeline: Transcriptome Profiling Studies of Influenza Susceptibility and Resistance

Excess or dysregulated host inflammatory responses cause much of the morbidity and mortality caused by severe influenza. Given the limitations of vaccines and antiviral drugs, novel therapeutics to modulate host responses and improve outcomes in severe influenza are needed. One strategy is to learn from the direct comparison of high-survivor versus high-mortality animal models. This review surveys the results of lung transcriptome profiling studies in murine models that directly compare susceptible versus resistant hosts challenged with identical influenza infections. The potential contributions and limitations of these studies are discussed. To amplify their power, the studies are subjected to a meta-analysis, which helps identify frequently dysregulated pathways and potentially novel areas for investigation. Using connectivity map-based tools (LINCS), transcriptome signatures linked to susceptibility can identify candidate drugs that merit testing for in vivo efficacy.