Respiratory and intestinal epithelial cells exhibit differential susceptibility and innate immune responses to EV-D68

  1. Megan Culler Freeman
  2. Alexandra I Wells
  3. Jessica Ciomperlik-Patton
  4. Michael M Myerburg
  5. Liheng Yang
  6. Jennifer Konopka-Anstadt
  7. Carolyn Coyne  Is a corresponding author
  1. University of Pittsburgh, United States
  2. Centers for Disease Control and Prevention, United States
  3. 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).

The following data sets were generated

Article and author information

Author details

  1. Megan Culler Freeman

    Pediatrics, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Alexandra I Wells

    Pediatrics, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jessica Ciomperlik-Patton

    Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael M Myerburg

    Medicine, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Liheng Yang

    Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jennifer Konopka-Anstadt

    Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Carolyn Coyne

    Duke University, Durham, United States
    For correspondence
    carolyn.coyne@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1884-6309

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.

Reviewing Editor

  1. Karla Kirkegaard, Stanford University School of Medicine, United States

Version history

  1. Received: January 19, 2021
  2. Accepted: June 30, 2021
  3. Accepted Manuscript published: July 1, 2021 (version 1)
  4. Version of Record published: July 16, 2021 (version 2)

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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  1. Megan Culler Freeman
  2. Alexandra I Wells
  3. Jessica Ciomperlik-Patton
  4. Michael M Myerburg
  5. Liheng Yang
  6. Jennifer Konopka-Anstadt
  7. Carolyn Coyne
(2021)
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

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https://doi.org/10.7554/eLife.66687

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