Antiviral function of type I and type III interferons in the olfactory epithelium
Background: The olfactory epithelium (OE) is one of the few sites where environmental pathogens can gain direct access to the brain. Despite this vulnerable arrangement, little is known about the protective mechanisms in the OE to prevent viral infection and subsequent entry into the brain. Methods: We systematically investigated acute responses in the olfactory mucosa (OM) upon exposure to vesicular stomatitis virus (VSV) by RNA-seq. VSVs were nasally inoculated into C57BL/6 mice. OM were dissected for gene expression analysis at different time points after viral inoculation. Interferon functions were determined by comparing viral gene expression in interferon (Ifn) receptor knockout (Ifnar1-/- and Ifnlr1-/-) with wildtype OM. Results: Antiviral responses were observed as early as 24hrs post viral exposure in the OM. Amongst the rapidly upregulated transcripts observed were specific type I as well as type III Ifns and interferon stimulated genes. Genetic analyses demonstrated that both type I and type III IFN signaling are required for the suppression of viral replication in the OM. Nasal IFNb1 or IFNl2 administration effectively reduces viral load in the OM. Conclusions: OE possesses innate ability to respond and suppress viral infection. Type I and type III IFNs actively participate in the OE's antiviral functions. Nasal IFN application effectively blocks viral replication in the OE suggesting therapeutic potential against viral insult. Overall design: Olfactory mucosa RNA samples obtained from different time points after nasal instillation of PBS or VSV were profiled by 3'tag RNA-seq