The RNA transcriptome of in vivo influenza virus infection reveals unique gene expression profiles in type 2 alveolar epithelial cells.

Globally, influenza virus outbreaks represent a serious threat to public health. Influenza virus infects type 2 alveolar epithelial cells (AEC) and utilizes cellular machinery in order to produce new infectious virions. During infection, multiple cell types release cytokines and other soluble factors that influence gene expression in both infected and uninfected cells. Here, the unique in vivo gene expression profiles between infected and uninfected bystander AEC from influenza virus infected mice are compared via next generation RNA-sequencing analysis. Mice were infected with PR8-expressing GFP virus (PR8-GFP). On day 3 post infection, GFP positive and negative AEC were FACS sorted from influenza virus infected mouse lungs. Transcriptome next generation RNA-sequencing analysis was performed comparing influenza-infected GFP-positive cells versus uninfected bystander GFP-negative cells from influenza virus-infected mouse lungs. Results from the sequencing data suggest a number of genes and associated pathways that are significantly differentially expressed in GFP-positive versus GFP-negative AEC. Pathways such as interferon signaling and cell death were found to be increased while Wnt signaling was decreased specifically within GFP-positive infected cells. RNA sequencing also identifies unique genes that are upregulated during virus infection, such as heatr9, that have yet to characterized during the response to influenza.