Club cells surviving influenza A virus infection induce temporary nonspecific antiviral immunity

Jennifer R. Hamilton, David Sachs, Jean K. Lim, Ryan A. Langlois, Peter Palese, Nicholas S. Heaton

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


A brief window of antigen-nonspecific protection has been observed after influenza A virus (IAV) infection. Although this temporary immunity has been assumed to be the result of residual nonspecific inflammation, this period of induced immunity has not been fully studied. Because IAV has long been characterized as a cytopathic virus (based on its ability to rapidly lyse most cell types in culture), it has been a forgone conclusion that directly infected cells could not be contributing to this effect. Using a Cre recombinase-expressing IAV, we have previously shown that club cells can survive direct viral infection. We show here not only that these cells can eliminate all traces of the virus and survive but also that they acquire a heightened antiviral response phenotype after surviving. Moreover, we experimentally demonstrate temporary nonspecific viral immunity after IAV infection and show that surviving cells are required for this phenotype. This work characterizes a virally induced modulation of the innate immune response that may represent a new mechanism to prevent viral diseases.

Original languageEnglish
Pages (from-to)3861-3866
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number14
StatePublished - 5 Apr 2016


  • Alternative cell fate
  • Antiviral immunity
  • Influenza virus
  • RNA sequencing


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