Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19

Urszula Radzikowska, Andrzej Eljaszewicz, Ge Tan, Nino Stocker, Anja Heider, Patrick Westermann, Silvio Steiner, Anita Dreher, Paulina Wawrzyniak, Beate Rückert, Juan Rodriguez-Coira, Damir Zhakparov, Mengting Huang, Bogdan Jakiela, Marek Sanak, Marcin Moniuszko, Liam O’Mahony, Marek Jutel, Tatiana Kebadze, David J. Jackson, Michael R. Edwards, Volker Thiel, Sebastian L. Johnston, Cezmi A. Akdis and Milena Sokolowska ()
Additional contact information
Urszula Radzikowska: University of Zurich
Andrzej Eljaszewicz: University of Zurich
Ge Tan: University of Zurich
Nino Stocker: University of Zurich
Anja Heider: University of Zurich
Patrick Westermann: University of Zurich
Silvio Steiner: Institute of Virology and Immunology (IVI)
Anita Dreher: University of Zurich
Paulina Wawrzyniak: University of Zurich
Beate Rückert: University of Zurich
Juan Rodriguez-Coira: University of Zurich
Damir Zhakparov: University of Zurich
Mengting Huang: University of Zurich
Bogdan Jakiela: Jagiellonian University Medical College
Marek Sanak: Jagiellonian University Medical College
Marcin Moniuszko: Medical University of Bialystok
Liam O’Mahony: University of Zurich
Marek Jutel: Wroclaw Medical University
Tatiana Kebadze: Imperial College London
David J. Jackson: King’s College London
Michael R. Edwards: Imperial College London
Volker Thiel: Institute of Virology and Immunology (IVI)
Sebastian L. Johnston: Imperial College London
Cezmi A. Akdis: University of Zurich
Milena Sokolowska: University of Zurich

Nature Communications, 2023, vol. 14, issue 1, 1-22

Abstract: Abstract Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium. Here, we show that rhinovirus infection in patients with asthma leads to an excessive RIG-I inflammasome activation, which diminishes its accessibility for type I/III interferon responses, leading to their early functional impairment, delayed resolution, prolonged viral clearance and unresolved inflammation in vitro and in vivo. Pre-exposure to house dust mite augments this phenomenon by inflammasome priming and auxiliary inhibition of early type I/III interferon responses. Prior infection with rhinovirus followed by SARS-CoV-2 infection augments RIG-I inflammasome activation and epithelial inflammation. Timely inhibition of the epithelial RIG-I inflammasome may lead to more efficient viral clearance and lower the burden of rhinovirus and SARS-CoV-2 infections.

Date: 2023
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DOI: 10.1038/s41467-023-37470-4

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