Rhinovirus-16 induced interferon response of nasal epithelium in viral clearance and asthma symptoms

Immunological mechanisms (English)

Ravi Ravi
Amsterdam University Medical Center, Respiratory Medicine and Experimental Immunology
BEKIJK PROGRAMMA
 
09 april 15:12 - 15:30 (Markgraaf 3)
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.
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