RSV and HMPV Infections in 3D Tissue Cultures: Mechanisms Involved in Virus-Host and Virus-Virus Interactions.

Johan Geiser,Samuel Constant,Manel Essaidi-Laziosi,Guy Boivin,Song Huang,Laurent Kaiser,Caroline Tapparel

doi:10.3390/v13010139

Johan Geiser, Samuel Constant + Show 5 more

Open Access

https://doi.org/10.3390/v13010139

Copy DOI

Abstract

Respiratory viral infections constitute a global public health concern. Among prevalent respiratory viruses, two pneumoviruses can be life-threatening in high-risk populations. In young children, they constitute the first cause of hospitalization due to severe lower respiratory tract diseases. A better understanding of their pathogenesis is still needed as there are no approved efficient anti-viral nor vaccine against pneumoviruses. We studied Respiratory Syncytial virus (RSV) and human Metapneumovirus (HMPV) in single and dual infections in three-dimensional cultures, a highly relevant model to study viral respiratory infections of the airway epithelium. Our investigation showed that HMPV is less pathogenic than RSV in this model. Compared to RSV, HMPV replicated less efficiently, induced a lower immune response, did not block cilia beating, and was more sensitive to IFNs. In dual infections, RSV-infected epithelia were less permissive to HMPV. By neutralizing IFNs in co-infection assays, we partially prevented HMPV inhibition by RSV and significantly increased the number of co-infected cells in the tissue. This suggests that interference in dual infection would be at least partly mediated by the host immune response. In summary, this work provides new insight regarding virus-host and virus-virus interactions of pneumoviruses in the airway epithelium. This could be helpful for the proper handling of at-risk patients.

Highlights

We showed that human Metapneumovirus (HMPV) is less pathogenic than Respiratory Syncytial virus (RSV); first based on their replication kinetics and capacity to induce host response in single infection; and second based on RSV ability to interfere with HMPV replication in dual infections
In order to compare ex vivo infections by pneumoviruses, MucilairTM tissues were inoculated with RSV and HMPV at an multiplicity of infection (MOI) of around 0.02
Immuno-staining images suggested that RSV and HMPV infections were contained at the apical surface of the airway epithelia tissues but without evidence of syncytia formation in the tissue even in areas where cells were grouped (Figure 1C)

Summary

Introduction

Two pneumoviruses can be life-threatening in high-risk populations In young children, they constitute the first cause of hospitalization due to severe lower respiratory tract diseases. We studied Respiratory Syncytial virus (RSV) and human Metapneumovirus (HMPV) in single and dual infections in three-dimensional cultures, a highly relevant model to study viral respiratory infections of the airway epithelium. By neutralizing IFNs in co-infection assays, we partially prevented HMPV inhibition by RSV and significantly increased the number of co-infected cells in the tissue This suggests that interference in dual infection would be at least partly mediated by the host immune response. There is no approved antiviral or vaccine against these two viruses (except ribavirin for RSV that is not highly effective) This might be a consequence of the poor understanding of their pathogenicity [4,5].

Methods

Results

Conclusion