Abstract

Background: Older people are known to have an increased risk of viral infection, which can result in higher morbidity and mortality than younger people. Human rhinoviruses (HRV) are one of major respiratory viruses to be involved in exacerbations of asthma and COPD, but treatment options remain limited. Understanding the mechanism(s) as to why older people are more susceptible is still unclear.

Aim: To assess the effect of age on HRV viral infection and clearance on well differentiated airway epithelium

Methods: Bronchial epithelial cells differentiated at air liquid interface (ALI) from 3 ?young? donors (mean age 26.3) and 3 ?old? (mean age 55.7) were infected with human rhinovirus (HRV16) for 10 days. Viral load in apical wash was calculated by TCID50, cytokine release measured by MSD and gene expression examined by qRT-PCR.

Results: Viral titre peaked at 24-hour post infection (hpi) in young ALIs but peaked higher and later (48hpi) in older ALIs. Virus clearance was quicker in younger ALIs, with complete clearance at day 7 in the young but by day 10 in the aged, with significantly more viruses being detected at 72 hpi (P<0.05). CXCL8 levels were higher at early time points post infection in the older ALIs. IFNA and IRF7 both trended towards being lower in the older ALIs compared to younger ALIs at baseline, and levels increased less 10 days past virial infection in the older ALIs.

Conclusion: Here, we show that ALIs from older donors have slower viral clearance, and this may be due to reduce interferon/interferon response gene expression. Increasing the activity of viral response genes may be a potential therapeutic target to induce viral clearance in older people.