Viral Disruption of Olfactory Progenitors Is Exacerbated in Allergic Mice

Abstract

Objectives:

Viral infection in the upper respiratory tract (URT) is a major cause of olfactory impairment. Allergic inflammation such as asthma or rhinosinusitis often exacerbates smell problems in patients with viral infections by a mechanism that remains unclear. Here, we examined the effects of allergic airway inflammation on the progression of virus infection and on olfactory lineage cell populations in a mouse model of respiratory syncytial virus (RSV) infection.

Methods:

Balb/c mice were immunized subcutaneously and intraperitoneally with cockroach antigen (CR) on day −22, then administrated intranasally with CR every 4 days from day −8 to day 0 to induce asthma and allergic inflammation (allergic mice). Allergic and control mice were infected intranasally with RSV line 19 on day 0. RSV-RNA in the nasal mucosa and olfactory bulb were quantified by reverse transcription polymerase chain reaction (RT-PCR). The numbers of OMP⁺ mature olfactory neurons (ORNs), Sox2⁺ olfactory progenitor cells (OPs), and CK5⁺ basal cells (BCs) were determined by immunohistochemical staining.

Results:

RSV-RNA rapidly decreased and became undetectable on day 14 in control mice, whereas RSV-RNA persisted over 14 days in allergic mice. There were no changes in OMP+ORN or CK5+BC numbers following RSV infection. In control mice, Sox2+OP numbers were significantly reduced on day 2 but recovered thereafter. In allergic mice, this decrease was more severe and prolonged.

Conclusions:

Allergic background impedes RSV clearance in the URT and exacerbates viral disruption of Sox2+OPs. These results provide novel insight into the mechanism underlying the exacerbation of virus-induced olfactory impairment in allergic airway inflammation.