IRE1 inhibitor [RNA-seq]

The role of the unfolded protein response (UPR) in the cellular innate response to RSV infection is not fully understood. To better the genomic targets for the IRE1-XBP1 pathway, RNA seq was conducted on RSV-infected small airway cells in the absence or presence of RSV infection and in the absence or presence of a selective IRE1a RNAse inhibitor. We identified expression changes in ~3.2K genes; of these, 279 required IRE1? and were enriched in IL-10 signaling and cytokine signaling pathways. These data indicate that IRE1a-XBP1s regulates genes important in epithelial mesenchymal transition, hexosamine biosynthesis and anti-viral signaling. Overall design: hSAECs were cultured. 4 replicates were mock infected with sucrose cushion buffer alone. Another 8 were infected with sucrose-purified RSV Long strain at a multiplicity of infection (MOI) of 1.0 for 24 h prior to harvest. Four of the RSV infected plates were treated with a selective IRE1a RNAse inhibitor, kinase-inhibiting RNase attenuator (KIRA)-8 added directly to the culture medium at a concentration of 10 microMolar. Total RNA was extracted and subjected to short read illumina sequencing.