Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses

James T. VanLeuven; Benjamin J. Ridenhour; Craig R. Miller; Tanya A. Miura

. CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/090936 doi: bioRxiv preprint independent expression of these genes, or induction by a type I IFN that was not represented on the 295 microarray. Coronaviruses are notorious for being able to replicate within cells without triggering type I IFN 296 responses, or delaying IFN induction until late in the replication cycle [34, [50] [51] [52] . Other studies have shown 297 that the IFN response to MHV-1 is a critical determinant of susceptibility. Severe disease in A/J mice 298 compared to C57Bl/6 mice correlates with lower type I IFNs detected in the lungs of A/J mice upon MHV-1 299 infection [6, 53] . Similarly, the expression of various type I IFNs in response to MHV-1 infection in vitro is 300 cell line-dependent [53] . Because the cell line we used, LA4, was derived from the lungs of A/He mice, we 301 would expect it to have a similar response as A/J mice. Thus the lack of type I IFNs induced by MHV-1 in 302 LA4 cells in vitro corresponds with pathogenesis observed in A/J mice in vivo.