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 language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Apr 5 2016|
Bibliographical noteFunding Information:
We acknowledge Virginia Gillespie for her expertise in scoring the lung sections, Carlos Rodriguez for assistance with the multiplexed cytokine analysis, Rebekah Dumm for assistance with microscopy, and Matthew Evans and Marion Sourisseau for their expertise and help with the generation of the retrotransduced H441 cell line. We also acknowledge the use of the Mount Sinai Microscopy Shared Resource Facility, the Genomics Core Facility, the Biorepository and Pathology Center of Research Excellence (CORE), and the Flow Cytometry Shared Resource Facility. This work was partially supported by HHSN272201400008C (P.P.), U19 AI109946 (P.P.), F31AI120648 (J.R.H.), and K22AI116509 (N.S.H.).
- Alternative cell fate
- Antiviral immunity
- Influenza virus
- RNA sequencing