Influenza virus infection induces new cell populations in the lung

Influenza viruses, despite causing acute disease, leave footprints behind after clearance from the host.

Go to the profile of Nicholas Heaton
Feb 15, 2019
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Some viral infections, such as those caused by influenza viruses, are characterized as acute, cytopathic infections, i.e. infected cells are killed either the invading pathogen or the host immune system.  Since influenza disease is self-limiting in vivo, and viral infection kills cells in vitro, it has been assumed that the acute nature of the infection is the result of all infected cells being cleared from the host. Previous studies however, have provided evidence that some seemingly “cytopathic” viral infections are more nuanced than previously appreciated, and that not all virally infected cells are eliminated from the host upon the resolution of viral disease. In this study, we set out to ask if cellular "survival" of viral infection is a stochastic event with no particular role in infection or if surviving cells somehow play an active role in viral disease.

Since no one had previously studied whether cells could survive influenza B virus (IBV) infection, we generated an IBV strain that expresses Cre recombinase to permanently activate a host reporter construct in infected cells. We found that a distinct population of ciliated-like epithelial cells survive IBV infection in the upper airways of mice and that not only do these cells survive, but they are transcriptionally and morphologically distinct from uninfected ciliated cells in the same lungs.  These data show that viral infection can induce long-term changes to cellular physiology, even though the virus is completely eliminated.  Using survivor cell depletion assays, we showed that the presence of these surviving cells sped up the recovery from infection. Our results suggest that cellular survival is an active part of the host response to limit the severity of virally-induced disease. 

Our study was focused on one strain of influenza B virus, but adds to a growing body of literature that suggests that the most appreciated outcome of viral infection, such as cellular death after a cytopathic viral infection, is not necessarily the only outcome.  We believe it is likely that many viral (and potentially other microbial) infections leave behind populations of cells that have been significantly altered by the pathogen in some way.  Future studies defining these populations of cells, as well as how they are changed and the resulting effects on pathogenesis, will lead to a more complete understanding of the mechanisms that both promote and limit disease.

Our full report on cellular survival after IBV infection can be found at: https://www.nature.com/articles/s41467-019-08617-z

Go to the profile of Nicholas Heaton

Nicholas Heaton

Assistant Professor, Duke University

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