Abstract
Respiratory Syncytial Virus (RSV) is a significant cause of respiratory tract infections, particularly affecting young children and the elderly. Why RSV results in asymptomatic or mild infections in some, and life-threatening bronchiolitis in others, remains poorly understood. Severe disease is thought to result from both direct viral damage and excessive immune activation and inflammation. RSV is able to modulate the immediate responses in infected cells, by evading innate antiviral immunity and interfering with cell death pathways that are activated to counteract infection. Currently, the knowledge on how RSV interferes with these protective responses upon infection, and how this might contribute to exaggerated disease is scattered. Most studies use lab strains, potentially lacking key evasion mechanisms and not representing currently circulating strains. It's not yet known if and how virus variability might lead to different immediate cellular responses upon infection, and if this could, at least partially, explain differences in RSV disease severity. This project aims to comprehensively investigate early responses to RSV infection, focusing on innate immunity and cell death pathways, by using a unique library of bona-fide clinical isolates and relevant hAEC cultures. Validation of the results will be done using RSV reverse genetics, and the translational value will be confirmed in a set of >100 nasal samples from RSV-infected infants with different disease severity.
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