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

Abstract

Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and acute flaccid myelitis (AFM) and is detected in patient respiratory samples and from stool and wastewater, suggesting both respiratory and enteric routes of transmission. Here, we used a panel of EV-D68 isolates, including a historical 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 an earlier isolate 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 some isolates have the potential to target both the human airway and gastrointestinal tracts.

The Human Nose Organoid Respiratory Virus Model: an Ex Vivo Human Challenge Model To Study Respiratory Syncytial Virus (RSV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pathogenesis and Evaluate Therapeutics

“…Another important pathogen in the current scenario is SARS-CoV-2, the causative organism of COVID-19. AO systems are known for the robustness to model respiratory viral infections such as SARS-CoV-2 ( 9 , 39 ), influenza virus ( 34 ), enterovirus ( 40 ), and other respiratory diseases ( 1 ). We tested the usefulness of our HNOs as an ex vivo culture system for studying two major human respiratory viruses—RSV and SARS-CoV-2.…”

The human nose organoid respiratory virus model: an ex-vivo human challenge model to study RSV and SARS-CoV-2 pathogenesis and evaluate therapeutics

“…Another most important pathogen in the current scenario is SARS-CoV-2, the causative organism of COVID-19. AO systems are known for the robustness to model respiratory viral infections such as SARS-CoV-2 [35,40], influenza virus [34], enterovirus [41], and other respiratory diseases [1]. We tested the usefulness of our HNOs as ex-vivo culture system for studying two major human respiratory viruses: RSV, and SARS-CoV-2.…”