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.
Highlights
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[1,2,3]
The main objective of this study was to perform a comparative analysis of transcriptomic signatures of infection among different major respiratory viruses (Influenza, hRSV and hMPV) in human reconstituted airway epithelial (HAE)
It is worth noting that only few studies have performed such comparison, most of time limited to two viruses or viruses within the same family, and with very specific and limited readouts[17,18,20,21]
Summary
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[1,2,3]. Both in-house and commercially available (i.e. Mucilair ) HAE models, composed of human primary ciliated columnar cells, mucus-secreting goblet and basal cells cultivated at the air-liquid interface, have been successfully used to study viral infections and evaluate antivirals[14,15,16,17]. The aim of the present study was to perform a comparative analysis of transcriptomic signatures of infection among different major respiratory viruses (Influenza, hRSV and hMPV) in HAE, in order to identify and experimentally validate both common and specific key cellular pathways. Beyond providing new data highlighting the interplay between respiratory viruses and the host cells, this study underlines the interest of using biologically relevant models such as reconstituted HAE as a good compromise between in vitro immortalized cell lines and ex-vivo/in-vivo experimental models for the functional study of respiratory pathogens
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