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

Louisa E. Sjaastad, Elizabeth J. Fay, Jessica K. Fiege, Marissa G. Macchietto, Ian A. Stone, Matthew W. Markman, Steven Shen, Ryan A. Langlois

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)9610-9615
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number38
StatePublished - Sep 18 2018

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. We thank Drs. Luis Martinez-Sobrido and Adolfo García-Sastre for reagents and Dr. Jason Mitchell and the Center for Immunology Imaging, the University of Minnesota Flow Cytometry Facility, and the Genomics Center for technical assistance. This work was supported by NIH K22 AI110581 and NIH R01 AI132962 (to R.A.L.), NIH T32 AI007313 (to E.J.F.), and NIH T32 HL007741 (to J.K.F.).


  • Influenza virus
  • Interferon-stimulated gene
  • Viral tropism

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