Early transcriptional responses to influenza virus infections in vivo

Abstract

Abstract Influenza A virus (IAV) infects a broad range of cell types within the respiratory tract. The cells initially targeted by the virus in a naïve host are the site of primary replication and virus spread. These cells are difficult to detect using replication competent IAV as the virus rapidly spreads to secondary cells. To overcome this obstacle we utilize a fluorescence expressing single cycle IAV (scIAV) to identify the cells initially infected in the mouse lung. Using this tool, we observed two distinct populations of epithelial cells during the early stages of infection: cells with high virus replication and cells with low virus replication. This suggests that some cells within the lung are innately permissive to virus replication while others are able to blunt replication. We have determined that this phenotype is not due to coinfection of a cell with multiple virions, and it appears to be independent of type I IFN. The level of replication is also not dependent on epithelial cell type. There are distinct cellular pathways that are significantly impacted in each population of infected cells compared to uninfected cells. Additionally, there are subsets of interferon-stimulated genes that are specifically upregulated in each population. These data indicate that different levels of virus replication may activate distinct cellular responses to infection. Fluorescent reporter scIAVs could be used to further elucidate the mechanism of cellular permissibility and the early innate immune response to IAV infection.