Rhinovirus-16 induced interferon response of nasal epithelium in viral clearance and asthma symptoms
Immunological mechanisms (English)Rationale: The temporal in vivo response of epithelial cells to an viral challenge and its association with viral clearance and clinical outcomes have been largely unexplored in asthma patients.
Objective: To determine gene expression profiles over time in nasal epithelial cells (NECs) challenged in vivo with rhinovirus-16 (RV16) and compare this to nasal symptoms and viral clearance.
Methods: Stable mild to moderate asthma patients (n=20) were challenged intranasally with RV16. Nasal brush samples for RNA sequencing were taken 7 days prior to infection and at day 3, 6 and 14 post-infection, and blood samples were taken 4 days prior to infection and on day 6 post-infection. Viral load was measured in nasal lavage fluid at day 3, 6 and 14.
Results: Top differentially (>2.5-fold increase) expressed gene sets in NECs were interferon alpha and gamma response genes at day 3 and 6, returning to near-baseline by day 14. Patients were classified as early resolvers (virus cleared by day 6), late resolvers (virus cleared by day 14) and non-resolvers (virus not cleared by day 14). Whereas the interferon response genes increased rapidly, but shortly (day 3 (p = 0.09) and 6 (p = 0.02)) in early resolvers, whereas in late resolvers these were significant increased at day 3, 6 and 14. Interestingly, non-resolvers had no enhanced interferon response genes in NECs on any of these days. The daily Cold Symptom Scores peaked at days 3 to 5 and correlated positively with the interferon response genes at day 3 (R=0.48), but not at other time points. Interferon response genes were also enhanced in blood at day 6 after RV16 challenge.
Conclusion: This study shows that viral load and clearance varies markedly over time in mild to moderate asthma patients exposed to a fixed RV16 dose. The host’s response to RV16-induced interferon determines symptoms and viral clearance in the nasal compartment.