Characterization of cellular transcriptomic signatures induced by different respiratory viruses in human reconstituted airway epithelia

Abstract : Acute respiratory infections, a large part being of viral origin, constitute a major public health issue. To propose alternative and/or new therapeutic approaches, it is necessary to increase our knowledge about the interactions between respiratory viruses and their primary cellular targets using the most biologically relevant experimental models. In this study, we used RNAseq to characterize and compare the transcriptomic signature of infection induced by different major respiratory viruses (Influenza viruses, hRSV and hMPV) in a model of reconstituted human airway epithelia. Our results confirm the importance of several cellular pathways commonly or specifically induced by these respiratory viruses, such as the innate immune response or antiviral defense. A very interesting common feature revealed by the global virogenomic signature shared between hRSV, hMPV and influenza viruses is the global downregulation of cilium-related gene expression, in good agreement with experimental evaluation of mucociliary clearance. Beyond providing new information about respiratory virus/host interactions, our study also underlines the interest of using biologically relevant experimental models to study human respiratory viruses. Acute respiratory infections (ARI) constitute a leading cause of acute illness worldwide and a major cause of death among young children, with nearly 2 million deaths per year 1-3. Among a panoply of different viral and bacterial pathogens, respiratory viruses, such as influenza A and B viruses (IAV and IBV), respiratory syncytial virus (hRSV-A and hRSV-B), human metapneumovirus (hMPV-A and hMPV-B) or rhinoviruses (RV), represent the main etiologic agents of these infections 2,4,5. In that regard, the limited or non-existent prophylactic and therapeutic arsenal available, coupled with the emergence of antiviral resistance, highlight the public health burden imposed by these respiratory pathogens. It appears therefore urgent to develop alternative and/or new therapeutic approaches, for which it is a necessary condition to increase our knowledge of the interactions between respiratory viruses and their primary cellular targets, namely respiratory epithelial cells. The last decade has witnessed the development of high-throughput "omics" approaches that have contributed to deepen our understanding of the multiple levels of interplay between respiratory viruses and the host cell. Numerous studies have described the impact of infection on host gene expression in vitro or in vivo, mainly in the context of influenza viruses or hRSV and to a lesser extent for other respiratory viruses such hMPV 6-10. For example , several mRNA profiling studies, including ours, have highlighted the role of NF-kB, p53, or MAPK cellular
Complete list of metadatas

Cited literature [44 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-02322305
Contributor : Olivier Terrier <>
Submitted on : Monday, October 21, 2019 - 3:45:17 PM
Last modification on : Tuesday, November 19, 2019 - 2:37:56 AM

File

Nicolas de Lamballerie et al. ...
Publication funded by an institution

Identifiers

Collections

Citation

Claire Nicolas de Lamballerie, Andres Pizzorno, Julia Dubois, Thomas Julien, Blandine Padey, et al.. Characterization of cellular transcriptomic signatures induced by different respiratory viruses in human reconstituted airway epithelia. Scientific Reports, Nature Publishing Group, 2019, 9 (1), ⟨10.1038/s41598-019-48013-7⟩. ⟨hal-02322305⟩

Share

Metrics

Record views

28

Files downloads

26