Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures

Publication date: Available online 8 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Manel Essaidi-Laziosi, Francisco Brito, Sacha Benaoudia, Léna Royston, Valeria Cagno, Mélanie Fernandes-Rocha, Isabelle Piuz, Evgeny Zdobnov, Song Huang, Samuel Constant, Marc-Olivier Boldi, Laurent Kaiser, Caroline Tapparel
BackgroundLeading etiologies of acute illnesses, respiratory viruses typically cause self-limited diseases, though severe complications can occur in fragile patients. Rhinoviruses, respiratory enteroviruses, influenza virus, respiratory syncytial viruses and coronaviruses are highly prevalent respiratory pathogens, but due to the lack of reliable animal models, their differential pathogenesis remains poorly characterized.ObjectiveTo compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia.MethodsTissues were infected with rhinoviruses RV-A55, RV-A49, RV-B48, RV-C8 and RV-C15, respiratory enterovirus EV-D68, influenza virus H3N2, respiratory syncytial virus RSV-B and coronavirus HCoV-OC43. Replication kinetics, cell tropism, impact on tissue integrity and cytokine secretion were compared. Virus adaptation and tissue response were assessed through RNA-sequencing.ResultsRhinoviruses, RSV-B and HCoV-OC43 infected ciliated cells and caused no major cell death while H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses except RV-B48 and HCoV-OC43 altered cilia beating and MCC. H3N2 was the strongest cytokine-inducer and HCoV-OC43 the weakest. Persistent infection was observed in all cases. RNA-sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4-days post-infection. No majority mutations emerged in the viral population.ConclusionOur results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection-phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory infections in immunocompromised hosts.

Teaser

Using reconstituted airway epithelia, we highlight marked differences in in vitro pathogenesis of respiratory viruses. In the absence of immune cells, we observe viral persistence linked to a contained tissue-response rather than to viral mutations.


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