Science and Research

Rhinovirus-16 induced temporal interferon responses in nasal epithelium links with viral clearance and symptoms

BACKGROUND: The temporal in vivo response of epithelial cells to a viral challenge and its association with viral clearance and clinical outcomes has been largely unexplored in asthma. OBJECTIVE: To determine gene expression profiles over time in nasal epithelial cells (NECs) challenged in vivo with rhinovirus-16 (RV16) and compare to nasal symptoms and viral clearance. METHODS: Patients with stable mild to moderate asthma (n = 20) were challenged intranasally with RV16. Nasal brush samples for RNA sequencing were taken 7 days prior to infection and 3, 6 and 14 days post-infection, and blood samples 4 days prior to infection and 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 post-RV16 at days 3 and 6, compared with baseline, were interferon alpha and gamma response genes. Patients clearing the virus within 6 days (early resolvers) had a significantly increased interferon response at day 6, whereas those having cleared the virus by day 14 (late resolvers) had significantly increased responses at day 3, 6 and 14. Interestingly, patients not having cleared the virus by day 14 (non-resolvers) had no enhanced interferon responses at any of these days. The daily Cold Symptom Scores (CSS) peaked at days 3 to 5 and correlated positively with 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 AND CLINICAL RELEVANCE: 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 nasal interferon response to RV16 at day 3 is associated with upper respiratory tract symptoms. The temporal interferon response in nasal epithelium associates with viral clearance in the nasal compartment.

  • Ravi, A.
  • Chang, M.
  • van de Pol, M.
  • Yang, S.
  • Aliprantis, A.
  • Thornton, B.
  • Carayannopoulos, L. N.
  • Bautmans, A.
  • Robberechts, M.
  • De Lepeleire, I.
  • Singh, D.
  • Hohlfeld, J. M.
  • Sterk, P. J.
  • Krug, N.
  • Lutter, R.
  • U. Biopred Study Group

Keywords

  • asthma
  • epithelium
  • innate immunity
  • interferon response
  • nasal epithelium
  • rhinovirus
  • virus
Publication details
DOI: 10.1111/cea.13481
Journal: Clin Exp Allergy
Pages: 1587-1597 
Number: 12
Work Type: Original
Location: BREATH
Disease Area: AA
Partner / Member: ITEM
Access-Number: 31400236
See publication on PubMed

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