E-GEOD-51267 - Temporal Transcriptomic Signatures Associated with Post-viral Bronchiolitis Sequelae in Rats
Released on 1 October 2013, last updated on 3 June 2014
Early life respiratory viral infections and atopic characteristics are significant risk factors for the development of childhood asthma. It is hypothesized that repeated respiratory viral infections might induce structural remodeling by interfering with the normal process of lung maturation; however, the specific molecular processes that mediate these developments are not understood. To define relevant molecular pathways, we used a well-established Sendai virus infection model in weanling rats to compare transcriptome signatures between a post-infection asthma prone susceptible strain (BN) and a post-infection asthma resistant strain (F344). Specific to this weanling model and not described in adult models, Sendai virus infection in the susceptible strain resulted in morphological abnormalities in distal airways that persist into adulthood, suggesting a disruption of normal lung growth. Gene expression data from infected and control lungs across five time points indicated that specific features of the immune response following viral infection were heightened and prolonged in lungs from BN compared with F344 rats. These features included an increase in macrophage cell number and related gene expression, which then transitioned to an increase in mast cell number and related gene expression. In contrast to the heightened immune response in infected BN lungs, infected F344 lungs displayed more efficient re-epithelialization. We conclude that the structural defects that developed and persisted in infected BN but not F344 lungs were preceded by a pronounced macrophage and mast cell response to viral infection acting in parallel with an inadequate re-epithelialization. For each of the five time points, one array was run for each of the four conditions (F344 control, BN control, F344 virus, BN virus) with 15 individual smaples pooled on each array.
transcription profiling by array
Xin Sun <email@example.com>, Elizabeth A Hines