Published on December 14, 2018 | Updated on December 14, 2018

ViBra-Flu Project

Virome-Bacteriome-Transcriptome interactions implicated in influenza pathogenesis in children

Co-leaders : Bruno Lina & Laurence Josset (CIRI) and Claire Bardel (LBBE)

Severe influenza is a multi-factorial process where complex interactions between host, viral and environmental factors determine disease outcome. These interactions are still poorly understood and influenza outcome is not predictable at the time of patient infection. Recent studies suggest that the respiratory microbiome is implicated in determining acute respiratory infections (ARI) incidence and severity. During influenza infection, the microbiome regulates the host immune response. Most of the studies about the microbiome have focused on its bacterial component and the composition and role of the respiratory virome during ARI is unknown. Interactions between viral and bacterial components of the microbiome, referred to as trans-kingdom interactions, are increasingly involved in health and disease but have not been defined in the respiratory tract yet.
Here we propose to characterize the role of trans-kingdom interactions within the respiratory microbiome involved in influenza pathogenesis and to define prognostic biomarkers of influenza.
To achieve this, we will use a prospective collection of respiratory samples from children infected with influenza virus and evolving to severe or benign influenza and we will characterize the virome and bacteriome compositions associated with severe and mild influenza, together with the respiratory transcriptomic host responses to infection. These data will be integrated with clinical data in order to define virome-bacteriome-host transcriptome interactions associated with severe influenza, and to identify combinatorial biomarkers of influenza disease outcome.

The ViBra-Flu project will lead to:
• Medical advances: This project will identify combinatorial signatures comprising virome, bacteriome and host transcriptome for predicting influenza outcome at hospital admission. Such prognostic biomarkers will improve the identification of patients with risk of severe disease and allow to develop risk-based strategies for enhanced care management. In the long term, these data may provide leads to develop innovative personalized therapy against severe influenza, by targeting deleterious interactions within the microbiome or specific microbial species.
• Scientific advances: Deciphering trans-kingdom relationships within the respiratory microbiome involved in influenza severity may lead to a better understanding of influenza pathogenesis and of the role of the microbiome in respiratory disease. In addition, this project will address methodological challenges both in bioinformatics, with the statistical comparison of virome analysis pipelines and their improvement, and biostatistics with the integration of high dimension and clinical data.

Co-leadersBruno Lina & Laurence Josset, team "Virologies et Pathologies humaines - VirPath" (CIRI) and Claire Bardel, team "Biostatistiques-santé" (LBBE).
Collaborative teams: Anne-Béatrice Dufour & Jean Thioulouse, team "Ecologie quantitative et évolutive des communautés" (LBBE), Vincent Navratil (PRABI) and Yves Gillet (Hôpital Femme-Mère-Enfant HCL, Lyon).
Project duration : 2 years
Financing :
PhD fellowship & consumable money
PhD fellow :
Marina Sabatier