Delineating the unique functions of type I and type III interferons during respiratory viral infections to develop new therapeutic interventions

The natural ability of a host to resolve virus infections largely depends on interferons (IFNs).

Yet, there is a lack of pre-clinical studies on how individual IFN members affect transcriptional and metabolic processes during infections of the respiratory tracts. Our goal is to determine how IFNs can be harnessed to protect the host against RNA viruses.

To do this, we will: i) Characterise in human cells and samples how the IFN landscape in the upper and lower airways determine transcriptional and metabolic changes during respiratory infections. ii) Assess in mice how specific IFNs dictate the host response against RNA virus infections of the respiratory tract.

In Year 1 we will use clinical samples from SARS-CoV-2 and Influenza A infected patients to characterise the IFN landscape, the induction of interferon stimulatory genes, and the metabolic changes in the upper and lower respiratory tracts via transcriptomic analyses.

Next, we will analyse in vitro how specific IFN modulates the transcriptional and metabolic responses of human lung epithelial cells and phagocytes grown at air liquid interphase.

In Years 2 and 3, we will use in vivo mouse models to assess the prophylactic or therapeutic potential of different IFN combinations during infection with SARS-CoV-2 or Influenza A.

This study will pave the way for the rational design of new therapeutic interventions aimed at using specific clinical grade IFNs against respiratory viruses that have the capacity to cause pandemics.