Comparative cross-species transcriptomics during RSV infection identifies targets to treat RSV disease

Respiratory syncytial virus (RSV) remains a health threat to young children worldwide. The host immune response plays a key role in disease following infection. Infection models advance our understanding of respiratory viruses, but individual models have gaps, which overlapping complementary systems can fill. We compared disease signatures in mice, adults and children; combining transcriptomic data collected from blood, nasal mucosa and lung biopsy following RSV infection. We identified both shared and species-specific pathways triggered by RSV. While systemic responses in children's blood were more similar to those in RSV-challenged adults, mucosal responses during primary infection in mice more closely resembled those in children. We identified an association between IL-17 pathways and RSV pathogenesis and with over-expression of the downstream effectors S100A8 and S100A9. Inhibiting these with the anti-inflammatory drug Paquinimod reduced disease. Here we demonstrate that integrating mouse and human transcriptomic data can identify novel targets to treat RSV disease.