dual infection; host receptors; innate immunity; pathogenesis; respiratory viruses
Essaidi-Laziosi Manel, Geiser Johan, Huang Song, Constant Samuel, Kaiser Laurent, Tapparel Caroline (2020), Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia, in Scientific Reports
, 10(1), 10246-10246.
Essaidi-Laziosi Manel, Brito Francisco, Benaoudia Sacha, Royston Léna, Cagno Valeria, Fernandes-Rocha Mélanie, Piuz Isabelle, Zdobnov Evgeny, Huang Song, Constant Samuel, Boldi Marc-Olivier, Kaiser Laurent, Tapparel Caroline (2018), Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures, in Journal of Allergy and Clinical Immunology
, 141(6), 2074-2084.
Royston Léna, Essaidi-Laziosi Manel, Pérez-Rodríguez Francisco J., Piuz Isabelle, Geiser Johan, Krause Karl-Heinz, Huang Song, Constant Samuel, Kaiser Laurent, Garcin Dominique, Tapparel Caroline (2018), Viral chimeras decrypt the role of enterovirus capsid proteins in viral tropism, acid sensitivity and optimal growth temperature, in PLOS Pathogens
, 14(4), e1006962-e1006962.
The human airway epithelium is the first line of defense against respiratory infections. Mucociliary clearance serves as a mechanical barrier against microorganisms while epithelial cells recognize and fight the infection via cytokine secretion. Viral respiratory infections are the most frequent causes of acute illnesses worldwide and cause mild to severe diseases such as common cold, bronchiolitis and pneumonia. Our project aims to study single and multiple viral infections by the most frequent human respiratory viruses using in vitro reconstituted human airway epithelia, a relevant model system mimicking the human respiratory epithelium. In the first achieved part, we infected in parallel, differentiated tissues with clinically relevant strains of rhinovirus, respiratory enterovirus, influenza virus, respiratory syncytial virus and coronavirus and different parameters were compared. For each virus, the replication kinetics, the cell tropism and the impact of the virus on tissue integrity and cytokine secretion was assessed. We showed that RVs, RSV-B and HCoV-OC43 infected only ciliated cells and caused no major cell death while H3N2 and EV-D68 caused massive ciliated cells loss, transient perturbation of tissue integrity and were detected in ciliated and non-ciliated cells. H3N2 was detected also in rare goblet and basal cells. All viruses except RV-B48 and HCoV-OC43 affected cilia beating and mucociliary clearance. Persistent replication was observed in all cases and was linked to moderate immune response rather than viral adaptation. This work provides insights on the different patterns of infection by the most prevalent respiratory viruses and on the interplay between the virus and the tissue response in the course of persistent infections. It was recently accepted for publication by Journal of Allergy and Clinical Immunology. In the second part of this project, we aim to study the consequences of multiple infections by distinct respiratory viruses in airway epithelia in terms of individual viral replication and tissue response. Preliminary data showed that Rhinovirus replication is inhibited by the presence of RSV-A and H1N1 but not HCoV-OC43 while H1N1 replication seems enhanced by a secondary RV infection. Deeper investigation is still needed in order to unveil the mechanism leading to virus-virus interactions. This study will provide important additional mechanistic clues regarding anti-viral innate immunity and virus pathogenesis and will help to handle optimally patients hospitalized with respiratory infections.