PNAS: Distinct antiviral signatures revealed by the magnitude and round of influenza virus replication in vivo

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[h=1]Distinct antiviral signatures revealed by the magnitude and round of influenza virus replication in vivo[/h] Louisa E. Sjaastad, Elizabeth J. Fay, Jessica K. Fiege, Marissa G. Macchietto, Ian A. Stone, Matthew W. Markman, Steven Shen, and Ryan A. Langlois
PNAS September 18, 2018 115 (38) 9610-9615; published ahead of print September 4, 2018 https://doi.org/10.1073/pnas.1807516115
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• Edited by Michael B. A. Oldstone, The Scripps Research Institute, La Jolla, CA, and approved August 8, 2018 (received for review May 9, 2018)
  [h=2]Significance[/h] Influenza A virus has a broad cellular tropism in the respiratory tract. Infected epithelial cells sense the infection and initiate an antiviral response. Here, we used single-cycle replication reporter viruses to analyze the early cellular response to influenza infection in vivo. This approach revealed distinct tiers of antiviral responses that were associated with the magnitude of virus replication. We also unveiled disparate protection of epithelial cell types mediated by interferon during virus spread. These results demonstrate the early landscape of virus?host interactions in vivo with the magnitude and round of replication revealing distinct antiviral signatures and responses.
  
  [h=2]Abstract[/h] Influenza 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 a series of single-cycle reporter viruses. These viral probes demonstrated cells in vivo harbor a range in magnitude of virus replication. Transcriptional profiling of cells supporting different levels of replication revealed tiers of IFN-stimulated gene expression. Uninfected cells and cells with blunted replication expressed a distinct and potentially protective antiviral signature, while cells with high replication expressed a unique reserve set of antiviral genes. Finally, we used these single-cycle reporter viruses to determine the antiviral landscape during virus spread, which unveiled disparate protection of epithelial cell subsets mediated by IFN in vivo. 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.
  
  http://www.pnas.org/content/115/38/9610