Optimize viral replication in primary human airway epithelial (HAE) cells for use in antiviral research to combat respiratory viral infections

This project focuses on exploring the use of HAE cultures to study the treatment of viral respiratory infections. HAE cultures will be used to evaluate novel antiviral strategies to combat Respiratory Syncytial Virus (RSV) infection and explore the kinetics of replication of different RSV virus strains. This will result in an optimized culture system to be used to characterize viral strains in a relevant ex vivo system and link viral factors with pathogenesis. Using HAE derived from healthy volunteers and COPD patients (provided by P12 (ES)), the role of RSV in exacerbations of COPD will be studied. Novel antiviral strategies will be evaluated in the RSV/HAE infection model. This will generate important information on the therapeutic potential of the different antiviral strategies, the risk of resistance development and the use of combination strategies. These results will be compared with results from existing animal studies with the aim to reduce the use of these animal models in the future. The role of inflammation in RSV pathology and the effect of antiviral strategies to recover the inflammation will be explored in collaboration with B3 (JU). A co-culture of HAE with immune cells obtained from healthy donors will be implemented and infected with several RSV strains. The cytokine profile of the co-cultures will be determined. During this project, we will focus on the following research objectives: - Optimize HAE culture system to study Respiratory Syncytial Virus (RSV) infections. - Proof-of-principle that the RSV/HAE can be used to characterize the potency of novel antiviral strategies including the characterization of resistance associated mutations. - Proof-of-principle that the co-culture of immune cells and HAE can be used to characterize the potency of novel antiviral strategies against RSV. This would mainly focus on the role of alveolar macrophages in pathology and replication of RSV. - Demonstrate that the HAE system can bring important contributions to the drug discovery/development pipeline for respiratory pathogens.