title: Viral disruption of olfactory progenitors is exacerbated in allergic mice.
abstract: Upper airway viral infection in patients with airway allergy often exacerbates olfactory dysfunction, but the mechanism for this exacerbation remains unclear. Here, we examined the effects of respiratory syncytial virus (RSV) infection, in the presence or absence of airway allergy, on olfactory receptor neurons (ORNs) and their progenitors in mice. Immunohistological analyses revealed that cockroach allergen (CRA)-induced airway allergy alone did not affect the number of OMP(+) mature ORNs and SOX2(+) ORN progenitors. Intranasal RSV line 19 infection in allergy-free mice resulted in a transient decrease in SOX2(+) ORN progenitors without affecting OMP(+) ORNs. In contrast, the RSV-induced decrease in SOX2(+) ORN progenitors was exacerbated and prolonged in allergic mice, which resulted in eventual loss of OMP(+) ORNs. In the allergic mice, reduction of RSV in the olfactory epithelium was delayed as compared with allergy-free mice. These results suggest that ORN progenitors were impaired by RSV infection and that airway allergy exacerbated damage to ORN progenitors by reducing viral clearance.
authors.affiliation: Department of Pathology, University of Michigan, United States; Department of Otolaryngology, University of Tokyo, Japan. Electronic address: ruu1025@yahoo.co.jp.
authors.forename: R
authors.initials: R
authors.lastname: Ueha
authors.affiliation: Department of Pathology, University of Michigan, United States.
authors.forename: S
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Pathology, University of Michigan, United States; Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo, Japan; CREST, Japan Science and Technology Agency, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ueha
authors.affiliation: Department of Pathology, University of Michigan, United States.
authors.forename: D E
authors.initials: DE
authors.lastname: de Almeida Nagata
authors.affiliation: Department of Otolaryngology, University of Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Otolaryngology, University of Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Otolaryngology, University of Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamasoba
authors.affiliation: Department of Pathology, University of Michigan, United States.
authors.forename: N W
authors.initials: NW
authors.lastname: Lukacs
authors.affiliation: Department of Pathology, University of Michigan, United States.
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D003058:Cockroaches; D005260:Female; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology* / Q000821:virology; D018034:Olfactory Receptor Neurons / Q000502:physiology* / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D019562:Viral Load
chemical_list: D000485:Allergens; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C060835:allergen CRa, cockroach
keywords: Airway allergy; Olfactory dysfunction; Olfactory receptor neuron; Respiratory syncytial virus; SOX2