Respiratory and intestinal epithelial cells exhibit differential susceptibility and innate immune responses to EV-D68
- University of Pittsburgh, United States
- Centers for Disease Control and Prevention, United States
- Duke University, United States
Abstract
Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and is associated with acute flaccid myelitis (AFM). EV-D68 is often detected in patient respiratory samples but has also been detected in stool and wastewater, suggesting the potential for both respiratory and enteric routes of transmission. Here, we used a panel of EV-D68 isolates, including a historical pre-2014 isolate and multiple contemporary isolates from AFM outbreak years, to define the dynamics of viral replication and the host response to infection in primary human airway cells and stem cell-derived enteroids. We show that some recent EV-D68 isolates have decreased sensitivity to acid and temperature compared with earlier isolates and that the respiratory, but not intestinal, epithelium induces a robust type III interferon (IFN) response that restricts infection. Our findings define the differential responses of the respiratory and intestinal epithelium to contemporary EV-D68 isolates and suggest that a subset of isolates have the potential to target both the human airway and gastrointestinal tracts.
Data availability
Raw sequencing files have been deposited in Sequence Read Archives and are publicly available (PRJNA688898).
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Author details
Funding
National Institute of Allergy and Infectious Diseases (AI081759)
- Carolyn Coyne
National Institute of Allergy and Infectious Diseases (AI060525)
- Alexandra I Wells
National Institute of Allergy and Infectious Diseases (AI149866)
- Alexandra I Wells
Pediatric Infectious Diseases Society (Fellowship in Basic and Translational Research)
- Megan Culler Freeman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Respiratory and intestinal epithelial cells exhibit differential susceptibility and innate immune responses to EV-D68
eLife 10:e66687.
https://doi.org/10.7554/eLife.66687
