BioProject

Influenza A virus has a broad cellular tropism in the respiratory tract. Infected epithelial cells sense the infection and initiate an antiviral response. More...

Influenza A virus has a broad cellular tropism in the respiratory tract. Infected epithelial cells sense the infection and initiate an antiviral response. To define the antiviral response at the earliest stages of infection we used two different single cycle replication reporter viruses. These tools demonstrated heterogeneity in virus replication levels in vivo. Transcriptional profiling demonstrated tiers of interferon stimulated gene responses that were dependent on the magnitude of virus replication. Uninfected cells and cells with blunted replication expressed a distinct and potentially protective ISG signature. Finally, we used these single cycle reporter viruses to determine the antiviral landscape during virus spread, which unveiled disparate protection mediated by IFN. Together these results highlight the complexity of virus-host interactions within the infected lung and suggest that magnitude and round of replication tune the antiviral response. Overall design: Mice were infected with 10^5 pfu of the indicated virus. Lungs from infefected C57BL/6 were taken at 24 hours post infection. Single cell suspensions were sorted for live CD45-CD31- and the indicated virus-driven fluorophore. Cells were FACS sorted directly into cell lysis buffer for RNA extraction. cDNA libraries were prepared using the SMARTer Universal Low Input RNA Kit (Takara Bio). SAmples were then profiled by illumina sequencing Less...